Panax notoginseng saponins(PNS)are a class of effective ingredients in Notoginseng Radix et Rhizoma,a well-known herbal medicine called San-Qi in Chinese.After oral administration,PNS inevitably interacts with gut mic...Panax notoginseng saponins(PNS)are a class of effective ingredients in Notoginseng Radix et Rhizoma,a well-known herbal medicine called San-Qi in Chinese.After oral administration,PNS inevitably interacts with gut microbiota,and thus affect the pharmacokinetic profiles and pharmacological effects.To date,studies concering gut microbiota-mediated metabolism of PNS have not been reviewed systematically.Herein,we outline the metabolic profiles of Panax notoginseng saponins mediated by gut microbiota,as well as its role in the pharmacokinetics and pharmacodynamics on the basis of reported data.The metabolic pathways of primary saponins are proposed,and step-by-step deglycosylation is found to be the primary degradation pathways of PNS mediated by gut microbiota.Specific microorganisms and enzymes involved in the metabolic processes were summarized.Gut microbiota is deeply involved in the metabolism of PNS,affects the pharmacokinetic profiles,and produces a series of active metabolites.These metabolites were documented to play an essential role in the efficacy of the parent compounds.Future studies should focus on strengthening the real-world evidence,defining the interaction between gut microbiota and PNS,and developing the strategy for modulating gut microbiota to enhance the bioavailability and efficacy of PNS.These information would be useful for further research and clinical application of PNS.展开更多
Objective:To investigate the mechanism of Fuyang Jiebiao granule(FYJBKL)in the treatment of viral pneumonia.Methods:Firstly,a network model was constructed using network pharmacology to study the target expression sit...Objective:To investigate the mechanism of Fuyang Jiebiao granule(FYJBKL)in the treatment of viral pneumonia.Methods:Firstly,a network model was constructed using network pharmacology to study the target expression sites of FYJBKL viral pneumonia,so as to determine the main targets and important signal transduction pathways for the treatment of viral pneumonia.Secondly,the main components of the drug and the main target are docked.Then,the fever,sweating and inflammation rat models were established to explore the antipyretic,sweating and anti-inflammatory mechanisms of FYJBKL.Finally,the contents of IL-17,IL-1β,TNF-αand IL-6 in blood samples of rats were analyzed by ELISA method,and the morphological changes of lung tissue were observed by HE staining.Results:Quercetin,luteolin,kaempferol,etc.,and the main mechanism targets are IL-17,IL-1β,TNF-α,IL-6 and so on.Thirty signal pathways were identified by KEGG enrichment analysis,including interleukin-17 signaling pathway(IL-17 signaling pathway),human cytomegalovirus infection pathway(human cytomegalovirus infection),Kaposi's sarcoma associated herpesvirus infection pathway(Kaposi's sarcoma-as-sociated herpesvirus infection)and so on.After the study of molecular docking,we found that the contact efficiency between active substances and possible key targets is good.The high and middle concentration groups of FYJBKL significantly decreased the expression of IL-17,IL-1β,TNF-αand IL-6 in the blood of rats with inflammation(P<0.05).FYJBKL significantly reduced the foot swelling induced by egg white and inhibited the increase of body temperature induced by yeast in rats(P<0.05).HE staining showed that FYJBKL improved pulmonary fibrosis and inflammatory exudation to varying degrees.Conclusion:The effects of FuyangJiebiao granules on the related signal pathways of anti-virus,anti-immune and anti-inflammation as well as biological and cellular processes may be caused by the binding of quercetin,luteolin,kaempferol and other active ingredients to their shared targets.Fuyang Jiebiao granules can improve the related symptoms caused by viral pneumonia,and its mechanism may be related to the activities of TNF,IL-17,IL-6 and other related channels,which are multiple targets of inflammation regulation.展开更多
[Objectives]To determine the optimal preparation technology of Clerodendrum bungei Steud.extract gel by orthogonal test and gel quality test method in General Rule 0114 of Chinese Pharmacopoeia(Volume IV,2020 Edition)...[Objectives]To determine the optimal preparation technology of Clerodendrum bungei Steud.extract gel by orthogonal test and gel quality test method in General Rule 0114 of Chinese Pharmacopoeia(Volume IV,2020 Edition),and to study its anorectal pharmacodynamics and drug release in vitro.[Methods]Carbomer 940,propylene glycol and absolute ethyl alcohol were selected as the main factors,and the preparation technology of C.bungei Steud.extract gel was optimized by orthogonal test.The mouse model of ulcerative hemorrhoids was established with glacial acetic acid(HAC)and compared with Ma Yinglong musk hemorrhoids ointment.The recovery of trauma was compared between the two groups.At the same time,porcine small intestine was used as semi-permeable membrane to make diffusion cell to simulate anal environment,and the drug release in vitro was studied.[Results]The C.bungei Steud.extract gel was smooth in appearance and good in stability.It could effectively treat anal ulcer in mice and release quickly in vitro.[Conclusions]The formula is reasonable,and the effect of animal experiment is remarkable,which can provide a new treatment plan for ulcerative hemorrhoids.展开更多
BACKGROUND Itraconazole is a broad-spectrum triazole antifungal inhibiting fungal growth by inhibiting ergosterol synthesis and exhibits a nonlinear pharmacokinetic profile.Erratic absorption pattern with wide fluctua...BACKGROUND Itraconazole is a broad-spectrum triazole antifungal inhibiting fungal growth by inhibiting ergosterol synthesis and exhibits a nonlinear pharmacokinetic profile.Erratic absorption pattern with wide fluctuations in blood levels causes inconsistent and unpredictable clinical behaviour of this drug despite its low minimum inhibitory concentration(MIC)as compared to other antifungal agents.AIM To compare the oral bioavailability and bioequivalence of Fixtral SB(supra bioavailable itraconazole)with reference product R2(supra bioavailable 2×50 mg itraconazole).METHODS The study population consisted of 54 healthy volunteers,aged between 18-45 years and randomized to receive a single oral dose of either test[T;Fixtral SB(supra bioavailable itraconazole)100 mg]or reference product(R1;Sporanox 100 mg×2 capsules and R2;Lozanoc capsules 50 mg×2 capsules).Blood samples were taken pre-dose and post-dose up to 96 h.The study evaluated bioequivalence by comparing the oral bioavailability of the test product with reference product R2.The pharmacodynamic characteristics of the drug were evaluated by comparing the test product with reference product R1.Pharmacokinetics(PK)-PD comparative analysis[area under the concentration-time curve(AUC)/minimum inhibitory concentration(MIC)>25]was performed for conventional itraconazole 100 mg and supra bioavailable itraconazole 50 mg.Adverse events(AEs)assessments were performed in each study period and post-study evaluation.RESULTS Statistical analysis of primary PK variables revealed bioequivalence,with confidence intervals being completely inside the acceptance criteria of 80%-125%.The peak concentration levels of itraconazole were achieved at 10 h(T)and 8.5 h(R2),respectively.Pharmacodynamic parameter assessment showed that AUC/MIC for R1 are comparable to Fixtral SB 100mg for MIC levels up to 16mcg/mL(P>0.05 and observed P=0.3196).Six AEs were observed that were mild to moderate in severity and resolved.No severe AE was reported.CONCLUSION Test product itraconazole Capsule 100 mg is bioequivalent with the reference product(R2)at 100 mg dose(2 capsules of Lozanoc®50 mg)under fed conditions.Pharmacodynamics activity in terms of AUC/MIC is comparable between the test product at 100 mg dose and marketed itraconazole 200 mg.Fixtral SB is expected to have therapeutically similar efficacy at half the equivalent dose.Tested formulations were found to be safe and well tolerated.展开更多
Background: The prevalence of both atrial fibrillation (FA) and diabetes mellitus (DM) is increasing and they often occur together and constitute a high risk of thrombosis. Rivaroxaban is a Factor Xa inhibitor with a ...Background: The prevalence of both atrial fibrillation (FA) and diabetes mellitus (DM) is increasing and they often occur together and constitute a high risk of thrombosis. Rivaroxaban is a Factor Xa inhibitor with a rapid onset and disappearance of action after oral administration;it acts by inhibiting the active form of the coagulation factor. In order to reflect the effect of the action of Rivaroxaban, we used the prothrombin time (PT);however, it′s not the most accurate, but it is the one available in our community. Methods: This was a prospective, randomized, analyst-blinded, parallel group clinical study to verify the efficacy of Rivaroxaban Leti 20 mg (RL) (12 volunteers vs Rivaroxaban Bayer 20 mg (RB) (13 volunteers). The variables were determination of PT and Partial Thromboplastin Time (aPTT) at baseline and at 24, 48 and 72 hours after administering a daily dose of 20 mg for three days. The determination was carried out with the IDG method (Integrated Diagnostics Group Sanzay Corporation) with an International Sensitivity Index (ISI) of 1.17 PT and aPTT were taken before the first dose, and then, every day during the next 3 days, three hours after the ingestion of their daily dose at 7 am. Results: The 25 healthy volunteers were similar in age, BMI, and SBP/DBP level with a greater number of men in the Bayer group. The efficacy of rivaroxaban was similar in both groups with prolongation of PTT to the 2nd day of treatment with PT, and percentage changes from baseline (14.46 ± 0.97 for RB vs 14.17 ± 0.94 RL p: 0.45), PTT results and percentage changes from the base (RB: 34 ± 4.53 RL: 33.46 ± 2.82). The safety of rivaroxaban was good in both groups with no serious adverse events. The equivalence in the logarithmically transformed PT result (ln) on day two, Mean and CI (90%) 99.2 (94.4-104) and 100 (99.5-100.8);neither the means nor the 90% confidence intervals of the PT variable transformed logarithmically to ensure its normality, were far from the 80%-125% allowed for declaration of similarity. Conclusion: The test formulation Rivaroxaban Asarap<sup>?</sup> 20 mg, manufactured by Leti Laboratories, is interchangeable or bioequivalent in clinical and laboratory response to the reference formulation Xarelto<sup>?</sup> manufactured by Bayer Laboratories.展开更多
Background:YangshenDingzhi granules(YSDZ)are clinically effective in preventing and treating COVID-19.The present study elucidates the underlying mechanism of YSDZ intervention in viral pneumonia by employing serum ph...Background:YangshenDingzhi granules(YSDZ)are clinically effective in preventing and treating COVID-19.The present study elucidates the underlying mechanism of YSDZ intervention in viral pneumonia by employing serum pharmacochemistry and network pharmacology.Methods:The chemical constituents of YSDZ in the blood were examined using ultraperformance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS).Potential protein targets were obtained from the SwissTargetPrediction database,and the target genes associated with viral pneumonia were identified using GeneCards,DisGeNET,and Online Mendelian Inheritance in Man(OMIM)databases.The intersection of blood component-related targets and disease-related targets was determined using Venny 2.1.Protein-protein interaction networks were constructed using the STRING database.The Metascape database was employed to perform enrichment analyses of Gene Ontology(GO)functions and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways for the targets,while the Cytoscape 3.9.1 software was utilized to construct drug-component-disease-target-pathway networks.Further,in vitro and in vivo experiments were performed to establish the therapeutic effectiveness of YSDZ against viral pneumonia.Results:Fifteen compounds and 124 targets linked to viral pneumonia were detected in serum.Among these,MAPK1,MAPK3,AKT1,EGFR,and TNF play significant roles.In vitro tests revealed that the medicated serum suppressed the replication of H1N1,RSV,and SARS-CoV-2 replicon.Further,in vivo testing analysis shows that YSDZ decreases the viral load in the lungs of mice infected with RSV and H1N1.Conclusion:The chemical constituents of YSDZ in the blood may elicit therapeutic effects against viral pneumonia by targeting multiple proteins and pathways.展开更多
With the continuous progress of science and technology,the research methods of pharmacodynamic substances in traditional Chinese medicine are developing,and the application of these methods in teaching is becoming mor...With the continuous progress of science and technology,the research methods of pharmacodynamic substances in traditional Chinese medicine are developing,and the application of these methods in teaching is becoming more and more extensive.By introducing these research methods into the classroom,teachers can help students to deeply understand the nature and mechanism of action of pharmacodynamic substances in traditional Chinese medicine,and improve their interest in and knowledge of traditional Chinese medicine.This paper introduces the definition of pharmacodynamic substances in traditional Chinese medicine,research methods,and their application in the teaching of traditional Chinese medicine analysis.展开更多
AIM To explore the pharmacokinetics and pharmacodynamics of Shengjiang decoction(SJD) in rats with acute pancreatitis(AP) for protecting against multiple organ injury.METHODS An AP model was established by retrograde ...AIM To explore the pharmacokinetics and pharmacodynamics of Shengjiang decoction(SJD) in rats with acute pancreatitis(AP) for protecting against multiple organ injury.METHODS An AP model was established by retrograde perfusion of 3.5% sodium taurocholate into the biliopancreatic duct, and a control group(CG) received 0.9% sodium chloride instead. Twelve male Sprague-Dawley rats were randomly divided into a CG treated with SJD(CG + SJD) and a model group treated with SJD(MG + SJD), both of which were orally administered with SJD(5 g/kg) 2 h after surgery. Blood samples were collected via the tail vein at 10, 20, and 40 min and 1, 2, 3, 4, 6, 8, and 12 h after a single dose of SJD to detect its main components using high-performance liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters were compared. In the pharmacodynamic experiment, 18 male SpragueDawley rats were randomly divided into a CG, an AP model group(MG), and an SJD treated AP group(SJDG). Serum amylase, lipase, and inflammatory cytokines were measured, and heart, lung, liver, spleen, pancreas, kidney, and intestine tissues were collected for pathological examination.RESULTS The MG + SJD displayed significantly shorter mean residence time(MRT) and higher clearance(CL) for emodin and aloe-emodin; significantly shorter time of maximum concentration and T1/2 and a lower area under curve(AUC) for aloe-emodin; a significantly higher AUC and lower CL for rhein; and longer MRT and lower CL for chrysophanol than the CG + SJD. In the pharmacodynamic experiment, the amylase, interleukin(IL)-6, IL-10, and tumor necrosis factor(TNF)-α levels in the MG were higher than those in the CG(P < 0.05). After the herbal decoction treatment, the SJDG had higher IL-10 and lower TNF-α levels than the MG(P < 0.05). The MG had the highest pathological scores, and the pathological scores of the lung, pancreas, kidney, and intestine in the SJDG were significantly lower than those in the MG(P < 0.05).CONCLUSION AP may have varying effects on the pharmacokinetics of the major SJD components in rats. SJD might alleviate pathological injuries of the lung, pancreas, kidney, and intestine in rats with AP via regulating pro-and antiinflammatory responses, which might guide the clinical application of SJD for AP treatment.展开更多
AIM To explore the pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction (DCQD) in the liver of rats with severe acute pancreatitis (SAP) based on an herbal recipe tissue pharmacology hypothesis. METHODS Heal...AIM To explore the pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction (DCQD) in the liver of rats with severe acute pancreatitis (SAP) based on an herbal recipe tissue pharmacology hypothesis. METHODS Healthy male Sprague-Dawley rats were randomly divided into a sham operation group (SOG); a model group (MG); and low-, median- and high-dose treatment groups (LDG, MDG, and HDG, respectively). Different dosages (6, 12 and 24 g/kg for the LDG, MDG, and HDG, respectively) of DCQD were administered to the rats with SAP. The tissue concentrations of aloeemodin, rhein, emodin, chrysophanol, honokiol, rheo chrysophanol, magnolol, hesperidin, naringenin and naringin in the liver of the treated rats were detected by high-performance liquid chromatography tandem mass spectrometry. Alanine transaminase (ALT) and aspartate transaminase (AST) in serum, inflammatory mediators in the liver and pathological scores were evaluated. RESULTS The major components of DCQD were detected in the liver, and their concentrations increased dose-dependently. The high dose of DCQD showed a maximal effect in ameliorating the pathological damages, decreasing the pro-inflammatory mediators tumor necrosis factor-a and interleukin (IL)-6 and increasing anti-inflammatory mediators IL-4 and IL-10 in the liver. The pathological scores in the pancreas for the MG were significantly higher than those for the SOG (P < 0.05). DCQD could reduce the pathological scores in the pancreas and liver of the rats with SAP, especially in the HDG. Compared to the SOG, the ALT and AST levels in serum were higher in the MG (P < 0.05), while there was no statistical difference in the MG and HDG. CONCLUSION DCQD could alleviate liver damage by altering the inflammatory response in rats with SAP based on the liver distribution of its components.展开更多
The ultimate goal of transplantation is the donor-specific immune tolerance, but at least in the first 15 to 20 years of this century, immunosuppressive agents are still the determinant of clinical outcome of transpla...The ultimate goal of transplantation is the donor-specific immune tolerance, but at least in the first 15 to 20 years of this century, immunosuppressive agents are still the determinant of clinical outcome of transplant recipients. Individualizing patient's immunosuppression to optimize the balance between therapeutic efficacy and the occurrence of adverse events poses a great challenge to physicians. DATA SOURCES:The data in this article were taken mostly from MEDLINE (2000-2004), part of which were from the research of the authors. RESULTS:Individualized immunosuppression remains a problem because of the narrow therapeutic index and wide inter- and intra-patient variation of commonly-used im- munosuppressants. Recent progress in study of pharmaco-kinetics and pharmacodynamics improved the clinical outcome of transplant recipients. More importantly, the emergence of pharmacogenomics might provide a promising and complementary tool for traditional therapeutic drug monitoring (TDM). CONCLUSIONS:Individualizing organ recipient's immunosuppression to balance the therapeutic efficacy and the adverse events represents a great challenge to transplant clinicians. Pharmacogenomics shows great promise for an interesting and hopefully better future.展开更多
Lignocaine is an essential drug on World Health Organisation essential drug list, considered efficacious, safe and cost-effective for any health-care system. Despite its ubiquitous use in medicine and surgery, there a...Lignocaine is an essential drug on World Health Organisation essential drug list, considered efficacious, safe and cost-effective for any health-care system. Despite its ubiquitous use in medicine and surgery, there are few detailed reviews of its pharmacokinetics and pharmacodynamics. Being an amide-type local anesthetic and Class 1b antiarrhythmic, lignocaine is most frequently used clinically for its anesthetic and antiarrhythmic benefits. However, lignocaine has important antinociceptive, immuno-modulating, and antiinflammatory properties. Information pertaining to the pharmacokinetics and pharmacodynamics of lignocaine was examined by performing a literature search of Pub Med, Embase and MEDLINE(via Ovid), pharmacology textbooks and online sources. We present a focused synopsis of lignocaine's pharmacological composition, indications for use and mechanisms of action, focusing on its anti-inflammatory, immuno-modulating and analgesia effects. In addition we review the dosing regimes and infusion kinetics of lignocaine in the clinical setting. Finally, we review the evidence for ligocaine's modulation of the inflammatory response during major surgery and its specific effects on cancer recurrence. These indirect effects of local anesthetics in tumor development may stem from the reduction of neuroendocrine responses to the stress response elicited by major surgery and tissue damage, enhanced preservation of immune-competence, in addition to opioid-sparing effects of modulating tumor growth.展开更多
The electrochemical behavior of trifluoperazine at decanethiol self-assembledmonolayer (SAM) modified gold electrodes (i. e. C_(10) H_(21) SH/Au) has been studied,Trifluoperazine can effectively accumulate on C_(10) H...The electrochemical behavior of trifluoperazine at decanethiol self-assembledmonolayer (SAM) modified gold electrodes (i. e. C_(10) H_(21) SH/Au) has been studied,Trifluoperazine can effectively accumulate on C_(10) H_(21) SH/Au electrodes and generate asensitive anodic peak at about 0.63 V (vs. SCE) in 0.05 mol/L pH 9.4 Na_2 B_4 O_7 buffer solution.Under the selected conditions, the anodic peak current was linear to trifluoperazine concentrationin the range of 5.0 X 10^(-7)-3.O X 10^(-3) mol/Lwith correlation coefficient of 0.997, thedetection limit was 3.0 X 10^(-5) mol/L. This method was applied to the determination oftrifluoperazine in drug samples and the recovery was 97.3%-104.0% It was found that sodium dodecylsulfate (SDS) could make the anodic peak current increase. In the presence of SDS, the peak at about0.63 V turned into two peaks, resulting from the change of the electrochemical mechanism.展开更多
The work aims to investigate the in vitro release,pharmacokinetics(PK),pharmacodynamics(PD)and PK-PD relationships of Salvianolic Acid B micro-porous osmotic pump pellets(SalB-MPOPs)in angina pectoris New Zealand Whit...The work aims to investigate the in vitro release,pharmacokinetics(PK),pharmacodynamics(PD)and PK-PD relationships of Salvianolic Acid B micro-porous osmotic pump pellets(SalB-MPOPs)in angina pectoris New Zealand White(NZW)rabbits,compared with those of SalB immediate-release pellets(SalB-IRPs).The SalB plasma concentrations and Superoxide dismutase levels(PD index)were recorded continuously at predetermined time interval after administration,and the related parameters were calculated by using Win-Nonlin software.The release profile of MPOPs was more sustained than that of IRPs.PK results indicated that the mean C_(max) was significantly lower,the SalB plasma concentrations were steadier,both area under concentration-time curve from 0 to 24 h(AUC_(0-24 h))and from 0 to infinity(AUC_(0-∞))were presented larger,and both the peak concentration time(T_(max))and mean residence time(MRT)were prolonged for MPOPs,as compared with those of IRPs.PD results suggested that peak drug effect(E_(max))was lower and the equilibration rate constant(k_(e0))between the central compartment and the effect compartment was higher of MPOPs vs.those of IRPs.PKePD relationships demonstrated that the effectconcentration-time(ECT)course of MPOPs was clockwise hysteresis loop,and that of IRPs was counter-clockwise hysteresis loop.Collectively,those results demonstrated that MPOPs were potential formulations in treating angina pectoris induced by atherosclerosis.展开更多
The property theory of Chinese materia medica is one of the foundations of traditional Chinese medicine.The property of Chinese materia medica(PCMM)is a multi-dimensional expression of the effect of Chinese materia me...The property theory of Chinese materia medica is one of the foundations of traditional Chinese medicine.The property of Chinese materia medica(PCMM)is a multi-dimensional expression of the effect of Chinese materia medica(CMM),and it is related to the clinical prescription that fully reflects the clinical effect evaluation of CMM in a holistic,systematic,and scientific way.This paper discusses the source,development,and application of the PCMM by considering not only the five dimensions that constitute the PCMM but also the recognition of the human body and disease as given in traditional Chinese medicine.This paper aims to provide theoretical guidance for the rational use and development of CMM.展开更多
[Objective] The paper was to study in vitro pharmacodynamics characteristics of florfenicol dual suspension emulsion (DSEF). [Method] The florfenicol injection (FI) was used as the control group, the minimal inhibitor...[Objective] The paper was to study in vitro pharmacodynamics characteristics of florfenicol dual suspension emulsion (DSEF). [Method] The florfenicol injection (FI) was used as the control group, the minimal inhibitory concentration (MIC), minimal bactericide concentration (MBC) and mutant selection window (MSW) of florfenicol dual suspension emulsion on 5 kinds of bacteria were determined. The post-antibiotic effect (PAE) and post-antibiotic sub-MIC effect (PASME) of Salmonella typhimurium were also measured. [Result] Compared with the ordinary injection, the MIC and MBC of florfenicol dual suspension emulsion on 5 kinds of bacteria showed no obvious changes. However, florfenicol dual suspension emulsion obviously narrowed MSW of 5 kinds of bacteria (P<0.01), which also significantly extended PAE and PASME of S. typhimurium (P<0.01). [Conclusion] The florfenicol dual suspension emulsion in vitro can reduce the probability of bacterial resistance, significantly prolong after effect time of antibiotics on bacteria, thereby effectively improving the antibacterial effect.展开更多
OBJECTIVE To compare the pharmacokinetics and pharmacodynamics of PEG30-rhG-CSF administered to beagle dogs at three different dosages with PEG20-rhG-CSF administered at one dosage, and to provide an experimental basi...OBJECTIVE To compare the pharmacokinetics and pharmacodynamics of PEG30-rhG-CSF administered to beagle dogs at three different dosages with PEG20-rhG-CSF administered at one dosage, and to provide an experimental basis for clinical trials.METHODS Beagle dogs received single, subcutaneous doses of PEG30-rhG-CSF at 100, 200 and 400 μg/kg or PEG20-rhG-CSF at 200 μg/kg. PEG30-rhG-CSF and PEG20-rhG-CSF concentrations in serum were analyzed using an enzymeqinked immunosorbent assay （ELISA）. WBC, ANC and PLT counts of whole blood samples were measured using fully automated analytic instrumentation. Pharmacokinetic and pharmacodynamic parameters were calculated using DAS 2.0 statistical analysis software.METHODS Beagle dogs received single, subcutaneous doses of PEG30-rhG-CSF at 100, 200 and 400 μg/kg or PEG20-rhG-CSF at 200μg/kg. PEG30-rhG-CSF and PEG20-rhG-CSF concentrations in serum were analyzed using an enzyme-linked immunosorbent assay （ELISA）. WBC, ANC and PLT counts of whole blood samples were measured using fully automated analytic instrumentation. Pharmacokinetic and pharmacodynamic parameters were calculated using DAS 2.0 statistical analysis software. RESULTS The pharmacokinetic parameters of PEG30-rhG-CSF calculated from the serum concentration data determined by ELISA were as follows： the mean elimination half-life （t1/2ke） was 40.6 h （33.5-45.4 h）; the mean time to reach peak concentration （Tmax） was 19.2 h （11.7-24.0 h）; the drug clearance from the serum （CL） was decreased with increasing doses; the peak concentration （Cmax） and the area under the serum concentration-time curve （AUC） were increased with increasing doses. For PEG20-rhG- CSF, the half-life was shorter （12 h） and Tmax was achieved much earlier （10 h） relative to PEG30-rhG-CSF. The AUC of PEG30- rhG-CSF was much greater than that of PEG20-rhG-CSF, and the relative bioavailability with a subcutaneous injection was 158.7%. Administration of single doses of PEG30-rhG-CSF resulted in substantial increases in the absolute The time to reach ANC （ANCTmax） neutrophil count （ANC）. was 72 h. The maximum observed absolute neutrophil counts （ANCmax） and the area over the baseline effect curve （AOBEC） was increased with increasing doses. The effect-elimination half-life （t1/2E） ranged from 60 h to 80 h after subcutaneous administration. The PLT count was slightly elevated 8-12 h after s.c. injection, and declined after 24 h. CONCLUSION The mean elimination half-life of PEG30-rhG- CSF was longer than that of PEG20-rhG-CSF at the same dose, and the other main pharmacokinetic and pharmacodynamic parameters of PEG30-rhG-CSF, including C ANCmax, AUC and AOBEC were much greater than those following PEG20-rhG-CSF injection.展开更多
Pharmacological studies demonstrated that paclitaxel (Zisu() was very active in the inhibition of the growth of human cancer cell panel including KB cells, HCT-8, A2780, and MCF-7 cells. The IC50 was as low as 0.0019,...Pharmacological studies demonstrated that paclitaxel (Zisu() was very active in the inhibition of the growth of human cancer cell panel including KB cells, HCT-8, A2780, and MCF-7 cells. The IC50 was as low as 0.0019, 0.0019, 0.0036 and 0.01 ( g/ml respectively. Experimental therapeutic studies indicated that paclitaxel(Zisu() significantly inhibited the growth of melanoma B-16, Walker carcinomsarcoma and heterotransplanted human ovarian cancer in nude mice. Biochemical pharmacological studies showed that paclitaxel (Zisu() could accelerate microtubule assembly and inhibit its deassembly; population in G1 was decreased while the cell population in G2+M phase was increased significantly. In addition, a polyploid cell population appeared. Pharmacokinetic studies demonstrated that the t1/2( was 0.12 h and t1/2( was 5.02 h when it was injected intravenously at a dose of 5 mg/kg in rats. The AUC, Vc and CLs were 11.82(( g.h)/ml, 0.50L/kg and 0.42L(h.kg) respectively.展开更多
Objective To investigate the antiviral activity of recombinant interferonα-2b suppository(IFNα-2b)in vivo and in vitro.Methods The cytopathic-effect inhibition assay was applied in this study to investigate the anti...Objective To investigate the antiviral activity of recombinant interferonα-2b suppository(IFNα-2b)in vivo and in vitro.Methods The cytopathic-effect inhibition assay was applied in this study to investigate the antiviral activity of this drug as well as yingtelong and axiluowei as positive control.The guinea pig model of vaginitis and skin infection caused by HSV-2 infection were established,treated with IFNα-2b suppository at dosages of 60000、180000、540000 IU,using IFNα-2b injection 180000 IU·kg-1 as controls.Score the pathological changes of appearance and skin,the virus activities of vaginal secretion and tissue sections of viginae were assayed after treatment.Results The TD50 of IFN α-2b and yingtelong for Vero cells was(>100)μg·mL-1 and(>100000)IU·mL-1,respectively.The IC50 of IFN α-2b and yingtelong and axiluowei for Herpes virus type 1 was(0.29±0.08)μg·mL-1 and(185.0±28.8)IU·mL-1 and(0.19±0.03)μg·mL-1,respectively.The mean scores for vaginal and skin lesion of the treated groups were lower than those of untreated group.Among these concentrations,the IFNα-2b suppository of 540000 IU·kg-1 group.Showed highest anti-viral activity.The virus activity in vaginal secretion of treated group was lower than that of untreated group too(P<0.01 or P<0.05).Tissue sections of viginae after treatment with IFNα-2b suppository showed significantly therapeutical effects on the degrees of vaginal lesion.At the same dosage,The anti-HSV activity of IFNα-2b suppository was also compared with IFNα-2b injection,the results showed that the activity of suppository of 540000 IU·kg-1 group was similar to that of the injection.Conclusions The IFNα-2b suppository has anti-viruses function both in vivo and in vitro.展开更多
Background:Pudilan Xiaoyan Oral Liquid(PDL),a famous traditional Chinese formula for treating acute and chronic inflammation.To evaluate the broad-spectrum antiviral effect of Pudilan Xiaoyan Oral Liquid,and provide a...Background:Pudilan Xiaoyan Oral Liquid(PDL),a famous traditional Chinese formula for treating acute and chronic inflammation.To evaluate the broad-spectrum antiviral effect of Pudilan Xiaoyan Oral Liquid,and provide a basis for clinical medication.Methods:Its inhibitory effect on different respiratory viruses was observed by cytopathic test.The potential mechanism of the anti-influenza effect was determined by neuraminidase activity.In order to observe the therapeutic effect of PDL on viral pneumonia caused by different respiratory viruses.The viral pneumonia model was established by nasal infection with different respiratory viruses,and then PDL was given Therapeutic and prophylactically to evaluate its pharmacodynamic activity in vivo.Results:The results of in vitro experiments showed that PDL had different inhibitory effects on cytopathic effects caused by different respiratory viruses.And it has obvious inhibitory effect on the neuraminidase activity of influenza A virus,which indicates that it exerts anti-influenza virus effect by inhibiting neuraminidase activity of influenza virus.The results in vivo showed that PDL exhibited an inhibitory effect on pulmonary index(PI)and effectively reduced the degree of lesions in the lungs.The lethal rate of mice was significantly decreased while survival time of mice was dramatically increased by PDL treatment in comparison to infection control,respectively.Conclusions:Our study demonstrates that PDL had a significant protection and treatment effect for respiratory virus infection in vitro and in vivo.展开更多
Pseudomonas aeruginosa remains an important pathogen. Our purpose was to determine the minimum inhibitory con-centration (MIC) and pharmacodynamic (PD) parameters predicting a positive response to therapy with piperac...Pseudomonas aeruginosa remains an important pathogen. Our purpose was to determine the minimum inhibitory con-centration (MIC) and pharmacodynamic (PD) parameters predicting a positive response to therapy with piperacil-lin-tazobactam. Medical records were retrospectively reviewed at 3 centers. Data were recorded to assess age, type of disease, renal function, weight (body mass), MIC, antimicrobial treatment, and clinical outcome. Success was response to piperacillin-tazobactam alone, or in combination with another active agent;failure was lack of response. Of 78 eva-luable patients, 63 responded (7 UTI;56 non-UTI) and 15 did not;26 responding received combination therapy and 37 monotherapy. Piperacillin-tazobactam treatment was successful in 53 of 63 of non-UTI disease with a MIC of ≤64/4 μg/mL, but in only 3 of 7 with a MIC of >64/4 μg/mL (P = 0.023);overall 9 of 10 infections by strains with MICs = 32 - 64 μg/mL had a successful outcome. Piperacillin estimated time above MIC at 20% separated those responding from those that did not (P = 0.019).展开更多
基金supported by Guangdong Basic and Applied Basic Research Foundation(No.2022A1515012039)Guangzhou Science and Technology Plan Project(No.2024A03J0360).
文摘Panax notoginseng saponins(PNS)are a class of effective ingredients in Notoginseng Radix et Rhizoma,a well-known herbal medicine called San-Qi in Chinese.After oral administration,PNS inevitably interacts with gut microbiota,and thus affect the pharmacokinetic profiles and pharmacological effects.To date,studies concering gut microbiota-mediated metabolism of PNS have not been reviewed systematically.Herein,we outline the metabolic profiles of Panax notoginseng saponins mediated by gut microbiota,as well as its role in the pharmacokinetics and pharmacodynamics on the basis of reported data.The metabolic pathways of primary saponins are proposed,and step-by-step deglycosylation is found to be the primary degradation pathways of PNS mediated by gut microbiota.Specific microorganisms and enzymes involved in the metabolic processes were summarized.Gut microbiota is deeply involved in the metabolism of PNS,affects the pharmacokinetic profiles,and produces a series of active metabolites.These metabolites were documented to play an essential role in the efficacy of the parent compounds.Future studies should focus on strengthening the real-world evidence,defining the interaction between gut microbiota and PNS,and developing the strategy for modulating gut microbiota to enhance the bioavailability and efficacy of PNS.These information would be useful for further research and clinical application of PNS.
基金Emergency Research Project for Novel Coronavirus(2019-nCoV)Prevention and Control in Shanxi Province(No.202003D31012/GZ)Jingfang Fuyang Key Laboratory of Shanxi Province(No.202104010910011)Shanxi Provincial Health Commission Key Laboratory Construction Project。
文摘Objective:To investigate the mechanism of Fuyang Jiebiao granule(FYJBKL)in the treatment of viral pneumonia.Methods:Firstly,a network model was constructed using network pharmacology to study the target expression sites of FYJBKL viral pneumonia,so as to determine the main targets and important signal transduction pathways for the treatment of viral pneumonia.Secondly,the main components of the drug and the main target are docked.Then,the fever,sweating and inflammation rat models were established to explore the antipyretic,sweating and anti-inflammatory mechanisms of FYJBKL.Finally,the contents of IL-17,IL-1β,TNF-αand IL-6 in blood samples of rats were analyzed by ELISA method,and the morphological changes of lung tissue were observed by HE staining.Results:Quercetin,luteolin,kaempferol,etc.,and the main mechanism targets are IL-17,IL-1β,TNF-α,IL-6 and so on.Thirty signal pathways were identified by KEGG enrichment analysis,including interleukin-17 signaling pathway(IL-17 signaling pathway),human cytomegalovirus infection pathway(human cytomegalovirus infection),Kaposi's sarcoma associated herpesvirus infection pathway(Kaposi's sarcoma-as-sociated herpesvirus infection)and so on.After the study of molecular docking,we found that the contact efficiency between active substances and possible key targets is good.The high and middle concentration groups of FYJBKL significantly decreased the expression of IL-17,IL-1β,TNF-αand IL-6 in the blood of rats with inflammation(P<0.05).FYJBKL significantly reduced the foot swelling induced by egg white and inhibited the increase of body temperature induced by yeast in rats(P<0.05).HE staining showed that FYJBKL improved pulmonary fibrosis and inflammatory exudation to varying degrees.Conclusion:The effects of FuyangJiebiao granules on the related signal pathways of anti-virus,anti-immune and anti-inflammation as well as biological and cellular processes may be caused by the binding of quercetin,luteolin,kaempferol and other active ingredients to their shared targets.Fuyang Jiebiao granules can improve the related symptoms caused by viral pneumonia,and its mechanism may be related to the activities of TNF,IL-17,IL-6 and other related channels,which are multiple targets of inflammation regulation.
基金Supported by National Natural Science Foundation of China(31671954)。
文摘[Objectives]To determine the optimal preparation technology of Clerodendrum bungei Steud.extract gel by orthogonal test and gel quality test method in General Rule 0114 of Chinese Pharmacopoeia(Volume IV,2020 Edition),and to study its anorectal pharmacodynamics and drug release in vitro.[Methods]Carbomer 940,propylene glycol and absolute ethyl alcohol were selected as the main factors,and the preparation technology of C.bungei Steud.extract gel was optimized by orthogonal test.The mouse model of ulcerative hemorrhoids was established with glacial acetic acid(HAC)and compared with Ma Yinglong musk hemorrhoids ointment.The recovery of trauma was compared between the two groups.At the same time,porcine small intestine was used as semi-permeable membrane to make diffusion cell to simulate anal environment,and the drug release in vitro was studied.[Results]The C.bungei Steud.extract gel was smooth in appearance and good in stability.It could effectively treat anal ulcer in mice and release quickly in vitro.[Conclusions]The formula is reasonable,and the effect of animal experiment is remarkable,which can provide a new treatment plan for ulcerative hemorrhoids.
文摘BACKGROUND Itraconazole is a broad-spectrum triazole antifungal inhibiting fungal growth by inhibiting ergosterol synthesis and exhibits a nonlinear pharmacokinetic profile.Erratic absorption pattern with wide fluctuations in blood levels causes inconsistent and unpredictable clinical behaviour of this drug despite its low minimum inhibitory concentration(MIC)as compared to other antifungal agents.AIM To compare the oral bioavailability and bioequivalence of Fixtral SB(supra bioavailable itraconazole)with reference product R2(supra bioavailable 2×50 mg itraconazole).METHODS The study population consisted of 54 healthy volunteers,aged between 18-45 years and randomized to receive a single oral dose of either test[T;Fixtral SB(supra bioavailable itraconazole)100 mg]or reference product(R1;Sporanox 100 mg×2 capsules and R2;Lozanoc capsules 50 mg×2 capsules).Blood samples were taken pre-dose and post-dose up to 96 h.The study evaluated bioequivalence by comparing the oral bioavailability of the test product with reference product R2.The pharmacodynamic characteristics of the drug were evaluated by comparing the test product with reference product R1.Pharmacokinetics(PK)-PD comparative analysis[area under the concentration-time curve(AUC)/minimum inhibitory concentration(MIC)>25]was performed for conventional itraconazole 100 mg and supra bioavailable itraconazole 50 mg.Adverse events(AEs)assessments were performed in each study period and post-study evaluation.RESULTS Statistical analysis of primary PK variables revealed bioequivalence,with confidence intervals being completely inside the acceptance criteria of 80%-125%.The peak concentration levels of itraconazole were achieved at 10 h(T)and 8.5 h(R2),respectively.Pharmacodynamic parameter assessment showed that AUC/MIC for R1 are comparable to Fixtral SB 100mg for MIC levels up to 16mcg/mL(P>0.05 and observed P=0.3196).Six AEs were observed that were mild to moderate in severity and resolved.No severe AE was reported.CONCLUSION Test product itraconazole Capsule 100 mg is bioequivalent with the reference product(R2)at 100 mg dose(2 capsules of Lozanoc®50 mg)under fed conditions.Pharmacodynamics activity in terms of AUC/MIC is comparable between the test product at 100 mg dose and marketed itraconazole 200 mg.Fixtral SB is expected to have therapeutically similar efficacy at half the equivalent dose.Tested formulations were found to be safe and well tolerated.
文摘Background: The prevalence of both atrial fibrillation (FA) and diabetes mellitus (DM) is increasing and they often occur together and constitute a high risk of thrombosis. Rivaroxaban is a Factor Xa inhibitor with a rapid onset and disappearance of action after oral administration;it acts by inhibiting the active form of the coagulation factor. In order to reflect the effect of the action of Rivaroxaban, we used the prothrombin time (PT);however, it′s not the most accurate, but it is the one available in our community. Methods: This was a prospective, randomized, analyst-blinded, parallel group clinical study to verify the efficacy of Rivaroxaban Leti 20 mg (RL) (12 volunteers vs Rivaroxaban Bayer 20 mg (RB) (13 volunteers). The variables were determination of PT and Partial Thromboplastin Time (aPTT) at baseline and at 24, 48 and 72 hours after administering a daily dose of 20 mg for three days. The determination was carried out with the IDG method (Integrated Diagnostics Group Sanzay Corporation) with an International Sensitivity Index (ISI) of 1.17 PT and aPTT were taken before the first dose, and then, every day during the next 3 days, three hours after the ingestion of their daily dose at 7 am. Results: The 25 healthy volunteers were similar in age, BMI, and SBP/DBP level with a greater number of men in the Bayer group. The efficacy of rivaroxaban was similar in both groups with prolongation of PTT to the 2nd day of treatment with PT, and percentage changes from baseline (14.46 ± 0.97 for RB vs 14.17 ± 0.94 RL p: 0.45), PTT results and percentage changes from the base (RB: 34 ± 4.53 RL: 33.46 ± 2.82). The safety of rivaroxaban was good in both groups with no serious adverse events. The equivalence in the logarithmically transformed PT result (ln) on day two, Mean and CI (90%) 99.2 (94.4-104) and 100 (99.5-100.8);neither the means nor the 90% confidence intervals of the PT variable transformed logarithmically to ensure its normality, were far from the 80%-125% allowed for declaration of similarity. Conclusion: The test formulation Rivaroxaban Asarap<sup>?</sup> 20 mg, manufactured by Leti Laboratories, is interchangeable or bioequivalent in clinical and laboratory response to the reference formulation Xarelto<sup>?</sup> manufactured by Bayer Laboratories.
基金supported by Key R&D Project in Shandong ProvinceChina(Grant number:2020CXGC010505)+2 种基金Qingdao Science and Technology Demonstration Program for the Benefit of the PeopleShandong ProvinceChina(Grant number:23-7-8-smjk-3-nsh)。
文摘Background:YangshenDingzhi granules(YSDZ)are clinically effective in preventing and treating COVID-19.The present study elucidates the underlying mechanism of YSDZ intervention in viral pneumonia by employing serum pharmacochemistry and network pharmacology.Methods:The chemical constituents of YSDZ in the blood were examined using ultraperformance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS).Potential protein targets were obtained from the SwissTargetPrediction database,and the target genes associated with viral pneumonia were identified using GeneCards,DisGeNET,and Online Mendelian Inheritance in Man(OMIM)databases.The intersection of blood component-related targets and disease-related targets was determined using Venny 2.1.Protein-protein interaction networks were constructed using the STRING database.The Metascape database was employed to perform enrichment analyses of Gene Ontology(GO)functions and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways for the targets,while the Cytoscape 3.9.1 software was utilized to construct drug-component-disease-target-pathway networks.Further,in vitro and in vivo experiments were performed to establish the therapeutic effectiveness of YSDZ against viral pneumonia.Results:Fifteen compounds and 124 targets linked to viral pneumonia were detected in serum.Among these,MAPK1,MAPK3,AKT1,EGFR,and TNF play significant roles.In vitro tests revealed that the medicated serum suppressed the replication of H1N1,RSV,and SARS-CoV-2 replicon.Further,in vivo testing analysis shows that YSDZ decreases the viral load in the lungs of mice infected with RSV and H1N1.Conclusion:The chemical constituents of YSDZ in the blood may elicit therapeutic effects against viral pneumonia by targeting multiple proteins and pathways.
基金Jiangsu Province Higher Education Teaching Reform Research Key Project“Research and Reform of Industry-Needed Pharmacy Engineering Talents Incubation Mode from the Perspective of Industry-Teaching Integration and Innovation Drive”(2023JSJG077)。
文摘With the continuous progress of science and technology,the research methods of pharmacodynamic substances in traditional Chinese medicine are developing,and the application of these methods in teaching is becoming more and more extensive.By introducing these research methods into the classroom,teachers can help students to deeply understand the nature and mechanism of action of pharmacodynamic substances in traditional Chinese medicine,and improve their interest in and knowledge of traditional Chinese medicine.This paper introduces the definition of pharmacodynamic substances in traditional Chinese medicine,research methods,and their application in the teaching of traditional Chinese medicine analysis.
基金Supported by the National Natural Science Foundation of China,No.81603519,No.81573857,and No.81374042
文摘AIM To explore the pharmacokinetics and pharmacodynamics of Shengjiang decoction(SJD) in rats with acute pancreatitis(AP) for protecting against multiple organ injury.METHODS An AP model was established by retrograde perfusion of 3.5% sodium taurocholate into the biliopancreatic duct, and a control group(CG) received 0.9% sodium chloride instead. Twelve male Sprague-Dawley rats were randomly divided into a CG treated with SJD(CG + SJD) and a model group treated with SJD(MG + SJD), both of which were orally administered with SJD(5 g/kg) 2 h after surgery. Blood samples were collected via the tail vein at 10, 20, and 40 min and 1, 2, 3, 4, 6, 8, and 12 h after a single dose of SJD to detect its main components using high-performance liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters were compared. In the pharmacodynamic experiment, 18 male SpragueDawley rats were randomly divided into a CG, an AP model group(MG), and an SJD treated AP group(SJDG). Serum amylase, lipase, and inflammatory cytokines were measured, and heart, lung, liver, spleen, pancreas, kidney, and intestine tissues were collected for pathological examination.RESULTS The MG + SJD displayed significantly shorter mean residence time(MRT) and higher clearance(CL) for emodin and aloe-emodin; significantly shorter time of maximum concentration and T1/2 and a lower area under curve(AUC) for aloe-emodin; a significantly higher AUC and lower CL for rhein; and longer MRT and lower CL for chrysophanol than the CG + SJD. In the pharmacodynamic experiment, the amylase, interleukin(IL)-6, IL-10, and tumor necrosis factor(TNF)-α levels in the MG were higher than those in the CG(P < 0.05). After the herbal decoction treatment, the SJDG had higher IL-10 and lower TNF-α levels than the MG(P < 0.05). The MG had the highest pathological scores, and the pathological scores of the lung, pancreas, kidney, and intestine in the SJDG were significantly lower than those in the MG(P < 0.05).CONCLUSION AP may have varying effects on the pharmacokinetics of the major SJD components in rats. SJD might alleviate pathological injuries of the lung, pancreas, kidney, and intestine in rats with AP via regulating pro-and antiinflammatory responses, which might guide the clinical application of SJD for AP treatment.
基金Supported by National Natural Science Foundation of China,No.81374042,No.81370091 and No.81573857
文摘AIM To explore the pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction (DCQD) in the liver of rats with severe acute pancreatitis (SAP) based on an herbal recipe tissue pharmacology hypothesis. METHODS Healthy male Sprague-Dawley rats were randomly divided into a sham operation group (SOG); a model group (MG); and low-, median- and high-dose treatment groups (LDG, MDG, and HDG, respectively). Different dosages (6, 12 and 24 g/kg for the LDG, MDG, and HDG, respectively) of DCQD were administered to the rats with SAP. The tissue concentrations of aloeemodin, rhein, emodin, chrysophanol, honokiol, rheo chrysophanol, magnolol, hesperidin, naringenin and naringin in the liver of the treated rats were detected by high-performance liquid chromatography tandem mass spectrometry. Alanine transaminase (ALT) and aspartate transaminase (AST) in serum, inflammatory mediators in the liver and pathological scores were evaluated. RESULTS The major components of DCQD were detected in the liver, and their concentrations increased dose-dependently. The high dose of DCQD showed a maximal effect in ameliorating the pathological damages, decreasing the pro-inflammatory mediators tumor necrosis factor-a and interleukin (IL)-6 and increasing anti-inflammatory mediators IL-4 and IL-10 in the liver. The pathological scores in the pancreas for the MG were significantly higher than those for the SOG (P < 0.05). DCQD could reduce the pathological scores in the pancreas and liver of the rats with SAP, especially in the HDG. Compared to the SOG, the ALT and AST levels in serum were higher in the MG (P < 0.05), while there was no statistical difference in the MG and HDG. CONCLUSION DCQD could alleviate liver damage by altering the inflammatory response in rats with SAP based on the liver distribution of its components.
文摘The ultimate goal of transplantation is the donor-specific immune tolerance, but at least in the first 15 to 20 years of this century, immunosuppressive agents are still the determinant of clinical outcome of transplant recipients. Individualizing patient's immunosuppression to optimize the balance between therapeutic efficacy and the occurrence of adverse events poses a great challenge to physicians. DATA SOURCES:The data in this article were taken mostly from MEDLINE (2000-2004), part of which were from the research of the authors. RESULTS:Individualized immunosuppression remains a problem because of the narrow therapeutic index and wide inter- and intra-patient variation of commonly-used im- munosuppressants. Recent progress in study of pharmaco-kinetics and pharmacodynamics improved the clinical outcome of transplant recipients. More importantly, the emergence of pharmacogenomics might provide a promising and complementary tool for traditional therapeutic drug monitoring (TDM). CONCLUSIONS:Individualizing organ recipient's immunosuppression to balance the therapeutic efficacy and the adverse events represents a great challenge to transplant clinicians. Pharmacogenomics shows great promise for an interesting and hopefully better future.
文摘Lignocaine is an essential drug on World Health Organisation essential drug list, considered efficacious, safe and cost-effective for any health-care system. Despite its ubiquitous use in medicine and surgery, there are few detailed reviews of its pharmacokinetics and pharmacodynamics. Being an amide-type local anesthetic and Class 1b antiarrhythmic, lignocaine is most frequently used clinically for its anesthetic and antiarrhythmic benefits. However, lignocaine has important antinociceptive, immuno-modulating, and antiinflammatory properties. Information pertaining to the pharmacokinetics and pharmacodynamics of lignocaine was examined by performing a literature search of Pub Med, Embase and MEDLINE(via Ovid), pharmacology textbooks and online sources. We present a focused synopsis of lignocaine's pharmacological composition, indications for use and mechanisms of action, focusing on its anti-inflammatory, immuno-modulating and analgesia effects. In addition we review the dosing regimes and infusion kinetics of lignocaine in the clinical setting. Finally, we review the evidence for ligocaine's modulation of the inflammatory response during major surgery and its specific effects on cancer recurrence. These indirect effects of local anesthetics in tumor development may stem from the reduction of neuroendocrine responses to the stress response elicited by major surgery and tissue damage, enhanced preservation of immune-competence, in addition to opioid-sparing effects of modulating tumor growth.
基金Supported by the National Natural Science Foundation of China (20173040)
文摘The electrochemical behavior of trifluoperazine at decanethiol self-assembledmonolayer (SAM) modified gold electrodes (i. e. C_(10) H_(21) SH/Au) has been studied,Trifluoperazine can effectively accumulate on C_(10) H_(21) SH/Au electrodes and generate asensitive anodic peak at about 0.63 V (vs. SCE) in 0.05 mol/L pH 9.4 Na_2 B_4 O_7 buffer solution.Under the selected conditions, the anodic peak current was linear to trifluoperazine concentrationin the range of 5.0 X 10^(-7)-3.O X 10^(-3) mol/Lwith correlation coefficient of 0.997, thedetection limit was 3.0 X 10^(-5) mol/L. This method was applied to the determination oftrifluoperazine in drug samples and the recovery was 97.3%-104.0% It was found that sodium dodecylsulfate (SDS) could make the anodic peak current increase. In the presence of SDS, the peak at about0.63 V turned into two peaks, resulting from the change of the electrochemical mechanism.
基金This study is financially supported by the major project of National Science and Technology of China for new drugs development(No.2009ZX09310-004)Jiangsu Province Ordinary College and University innovative research programs(No.CX10B-374Z).
文摘The work aims to investigate the in vitro release,pharmacokinetics(PK),pharmacodynamics(PD)and PK-PD relationships of Salvianolic Acid B micro-porous osmotic pump pellets(SalB-MPOPs)in angina pectoris New Zealand White(NZW)rabbits,compared with those of SalB immediate-release pellets(SalB-IRPs).The SalB plasma concentrations and Superoxide dismutase levels(PD index)were recorded continuously at predetermined time interval after administration,and the related parameters were calculated by using Win-Nonlin software.The release profile of MPOPs was more sustained than that of IRPs.PK results indicated that the mean C_(max) was significantly lower,the SalB plasma concentrations were steadier,both area under concentration-time curve from 0 to 24 h(AUC_(0-24 h))and from 0 to infinity(AUC_(0-∞))were presented larger,and both the peak concentration time(T_(max))and mean residence time(MRT)were prolonged for MPOPs,as compared with those of IRPs.PD results suggested that peak drug effect(E_(max))was lower and the equilibration rate constant(k_(e0))between the central compartment and the effect compartment was higher of MPOPs vs.those of IRPs.PKePD relationships demonstrated that the effectconcentration-time(ECT)course of MPOPs was clockwise hysteresis loop,and that of IRPs was counter-clockwise hysteresis loop.Collectively,those results demonstrated that MPOPs were potential formulations in treating angina pectoris induced by atherosclerosis.
基金This study was supported by the National Natural Science Foundation of China(81430094)。
文摘The property theory of Chinese materia medica is one of the foundations of traditional Chinese medicine.The property of Chinese materia medica(PCMM)is a multi-dimensional expression of the effect of Chinese materia medica(CMM),and it is related to the clinical prescription that fully reflects the clinical effect evaluation of CMM in a holistic,systematic,and scientific way.This paper discusses the source,development,and application of the PCMM by considering not only the five dimensions that constitute the PCMM but also the recognition of the human body and disease as given in traditional Chinese medicine.This paper aims to provide theoretical guidance for the rational use and development of CMM.
文摘[Objective] The paper was to study in vitro pharmacodynamics characteristics of florfenicol dual suspension emulsion (DSEF). [Method] The florfenicol injection (FI) was used as the control group, the minimal inhibitory concentration (MIC), minimal bactericide concentration (MBC) and mutant selection window (MSW) of florfenicol dual suspension emulsion on 5 kinds of bacteria were determined. The post-antibiotic effect (PAE) and post-antibiotic sub-MIC effect (PASME) of Salmonella typhimurium were also measured. [Result] Compared with the ordinary injection, the MIC and MBC of florfenicol dual suspension emulsion on 5 kinds of bacteria showed no obvious changes. However, florfenicol dual suspension emulsion obviously narrowed MSW of 5 kinds of bacteria (P<0.01), which also significantly extended PAE and PASME of S. typhimurium (P<0.01). [Conclusion] The florfenicol dual suspension emulsion in vitro can reduce the probability of bacterial resistance, significantly prolong after effect time of antibiotics on bacteria, thereby effectively improving the antibacterial effect.
基金National High Technology Research and Development Program of China(No.2007BAI14IB04)Major State Basic Research Development Program(No.2004CB518902)
文摘OBJECTIVE To compare the pharmacokinetics and pharmacodynamics of PEG30-rhG-CSF administered to beagle dogs at three different dosages with PEG20-rhG-CSF administered at one dosage, and to provide an experimental basis for clinical trials.METHODS Beagle dogs received single, subcutaneous doses of PEG30-rhG-CSF at 100, 200 and 400 μg/kg or PEG20-rhG-CSF at 200 μg/kg. PEG30-rhG-CSF and PEG20-rhG-CSF concentrations in serum were analyzed using an enzymeqinked immunosorbent assay （ELISA）. WBC, ANC and PLT counts of whole blood samples were measured using fully automated analytic instrumentation. Pharmacokinetic and pharmacodynamic parameters were calculated using DAS 2.0 statistical analysis software.METHODS Beagle dogs received single, subcutaneous doses of PEG30-rhG-CSF at 100, 200 and 400 μg/kg or PEG20-rhG-CSF at 200μg/kg. PEG30-rhG-CSF and PEG20-rhG-CSF concentrations in serum were analyzed using an enzyme-linked immunosorbent assay （ELISA）. WBC, ANC and PLT counts of whole blood samples were measured using fully automated analytic instrumentation. Pharmacokinetic and pharmacodynamic parameters were calculated using DAS 2.0 statistical analysis software. RESULTS The pharmacokinetic parameters of PEG30-rhG-CSF calculated from the serum concentration data determined by ELISA were as follows： the mean elimination half-life （t1/2ke） was 40.6 h （33.5-45.4 h）; the mean time to reach peak concentration （Tmax） was 19.2 h （11.7-24.0 h）; the drug clearance from the serum （CL） was decreased with increasing doses; the peak concentration （Cmax） and the area under the serum concentration-time curve （AUC） were increased with increasing doses. For PEG20-rhG- CSF, the half-life was shorter （12 h） and Tmax was achieved much earlier （10 h） relative to PEG30-rhG-CSF. The AUC of PEG30- rhG-CSF was much greater than that of PEG20-rhG-CSF, and the relative bioavailability with a subcutaneous injection was 158.7%. Administration of single doses of PEG30-rhG-CSF resulted in substantial increases in the absolute The time to reach ANC （ANCTmax） neutrophil count （ANC）. was 72 h. The maximum observed absolute neutrophil counts （ANCmax） and the area over the baseline effect curve （AOBEC） was increased with increasing doses. The effect-elimination half-life （t1/2E） ranged from 60 h to 80 h after subcutaneous administration. The PLT count was slightly elevated 8-12 h after s.c. injection, and declined after 24 h. CONCLUSION The mean elimination half-life of PEG30-rhG- CSF was longer than that of PEG20-rhG-CSF at the same dose, and the other main pharmacokinetic and pharmacodynamic parameters of PEG30-rhG-CSF, including C ANCmax, AUC and AOBEC were much greater than those following PEG20-rhG-CSF injection.
文摘Pharmacological studies demonstrated that paclitaxel (Zisu() was very active in the inhibition of the growth of human cancer cell panel including KB cells, HCT-8, A2780, and MCF-7 cells. The IC50 was as low as 0.0019, 0.0019, 0.0036 and 0.01 ( g/ml respectively. Experimental therapeutic studies indicated that paclitaxel(Zisu() significantly inhibited the growth of melanoma B-16, Walker carcinomsarcoma and heterotransplanted human ovarian cancer in nude mice. Biochemical pharmacological studies showed that paclitaxel (Zisu() could accelerate microtubule assembly and inhibit its deassembly; population in G1 was decreased while the cell population in G2+M phase was increased significantly. In addition, a polyploid cell population appeared. Pharmacokinetic studies demonstrated that the t1/2( was 0.12 h and t1/2( was 5.02 h when it was injected intravenously at a dose of 5 mg/kg in rats. The AUC, Vc and CLs were 11.82(( g.h)/ml, 0.50L/kg and 0.42L(h.kg) respectively.
文摘Objective To investigate the antiviral activity of recombinant interferonα-2b suppository(IFNα-2b)in vivo and in vitro.Methods The cytopathic-effect inhibition assay was applied in this study to investigate the antiviral activity of this drug as well as yingtelong and axiluowei as positive control.The guinea pig model of vaginitis and skin infection caused by HSV-2 infection were established,treated with IFNα-2b suppository at dosages of 60000、180000、540000 IU,using IFNα-2b injection 180000 IU·kg-1 as controls.Score the pathological changes of appearance and skin,the virus activities of vaginal secretion and tissue sections of viginae were assayed after treatment.Results The TD50 of IFN α-2b and yingtelong for Vero cells was(>100)μg·mL-1 and(>100000)IU·mL-1,respectively.The IC50 of IFN α-2b and yingtelong and axiluowei for Herpes virus type 1 was(0.29±0.08)μg·mL-1 and(185.0±28.8)IU·mL-1 and(0.19±0.03)μg·mL-1,respectively.The mean scores for vaginal and skin lesion of the treated groups were lower than those of untreated group.Among these concentrations,the IFNα-2b suppository of 540000 IU·kg-1 group.Showed highest anti-viral activity.The virus activity in vaginal secretion of treated group was lower than that of untreated group too(P<0.01 or P<0.05).Tissue sections of viginae after treatment with IFNα-2b suppository showed significantly therapeutical effects on the degrees of vaginal lesion.At the same dosage,The anti-HSV activity of IFNα-2b suppository was also compared with IFNα-2b injection,the results showed that the activity of suppository of 540000 IU·kg-1 group was similar to that of the injection.Conclusions The IFNα-2b suppository has anti-viruses function both in vivo and in vitro.
基金supported by the National Natural Science Foundation of China(No.81774204)Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(No.CI2021A04608)。
文摘Background:Pudilan Xiaoyan Oral Liquid(PDL),a famous traditional Chinese formula for treating acute and chronic inflammation.To evaluate the broad-spectrum antiviral effect of Pudilan Xiaoyan Oral Liquid,and provide a basis for clinical medication.Methods:Its inhibitory effect on different respiratory viruses was observed by cytopathic test.The potential mechanism of the anti-influenza effect was determined by neuraminidase activity.In order to observe the therapeutic effect of PDL on viral pneumonia caused by different respiratory viruses.The viral pneumonia model was established by nasal infection with different respiratory viruses,and then PDL was given Therapeutic and prophylactically to evaluate its pharmacodynamic activity in vivo.Results:The results of in vitro experiments showed that PDL had different inhibitory effects on cytopathic effects caused by different respiratory viruses.And it has obvious inhibitory effect on the neuraminidase activity of influenza A virus,which indicates that it exerts anti-influenza virus effect by inhibiting neuraminidase activity of influenza virus.The results in vivo showed that PDL exhibited an inhibitory effect on pulmonary index(PI)and effectively reduced the degree of lesions in the lungs.The lethal rate of mice was significantly decreased while survival time of mice was dramatically increased by PDL treatment in comparison to infection control,respectively.Conclusions:Our study demonstrates that PDL had a significant protection and treatment effect for respiratory virus infection in vitro and in vivo.
文摘Pseudomonas aeruginosa remains an important pathogen. Our purpose was to determine the minimum inhibitory con-centration (MIC) and pharmacodynamic (PD) parameters predicting a positive response to therapy with piperacil-lin-tazobactam. Medical records were retrospectively reviewed at 3 centers. Data were recorded to assess age, type of disease, renal function, weight (body mass), MIC, antimicrobial treatment, and clinical outcome. Success was response to piperacillin-tazobactam alone, or in combination with another active agent;failure was lack of response. Of 78 eva-luable patients, 63 responded (7 UTI;56 non-UTI) and 15 did not;26 responding received combination therapy and 37 monotherapy. Piperacillin-tazobactam treatment was successful in 53 of 63 of non-UTI disease with a MIC of ≤64/4 μg/mL, but in only 3 of 7 with a MIC of >64/4 μg/mL (P = 0.023);overall 9 of 10 infections by strains with MICs = 32 - 64 μg/mL had a successful outcome. Piperacillin estimated time above MIC at 20% separated those responding from those that did not (P = 0.019).
