AIM To compare vonoprazan 10 and 20 mg vs lansoprazole 15 mg as maintenance therapy in healed erosive esophagitis(EE).METHODS A total of 607 patients aged ≥ 20 years, with endoscopically-confirmed healed EE following...AIM To compare vonoprazan 10 and 20 mg vs lansoprazole 15 mg as maintenance therapy in healed erosive esophagitis(EE).METHODS A total of 607 patients aged ≥ 20 years, with endoscopically-confirmed healed EE following 8 wk of treatment with vonoprazan 20 mg once daily, were randomized 1:1:1 to receive lansoprazole 15 mg(n = 201), vonoprazan 10 mg(n = 202), or vonoprazan 20 mg(n = 204), once daily. The primary endpoint of the study was the rate of endoscopically-confirmed EE recurrence during a 24-wk maintenance period. The secondary endpoint was the EE recurrence rate at Week 12 during maintenance treatment. Additional efficacy endpoints included the incidence of heartburn and acid reflux, and the EE healing rate 4 wk after the initiation of maintenance treatment. Safety endpoints comprised adverse events(AEs), vital signs, electrocardiogram findings, clinical laboratory results, serum gastrin and pepsinogen Ⅰ/Ⅱ levels, and gastric mucosa histopathology results.RESULTS Rates of EE recurrence during the 24-wk maintenance period were 16.8%, 5.1%, and 2.0% with lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg, respectively. Vonoprazan was shown to be non-inferior to lansoprazole 15 mg(P < 0.0001 for both doses). In a post-hoc analysis, EE recurrence at Week 24 was significantly reduced with vonoprazan at both the 10 mg and the 20 mg dose vs lansoprazole 15 mg(5.1% vs 16.8%, P = 0.0002, and 2.0% vs 16.8%, P < 0.0001, respectively); by contrast, the EE recurrence rate did not differ significantly between the two doses of vonoprazan(P = 0.1090). The safety profiles of vonoprazan 10 and 20 mg were similar to that of lansoprazole 15 mg in patients with healed EE. Treatment-related AEs were reported in 11.4%, 10.4%, and 10.3% of patients in the lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg arms, respectively.CONCLUSION Our findings confirm the non-inferiority of vonoprazan 10 and 20 mg to lansoprazole 15 mg as maintenance therapy for patients with healed EE.展开更多
AIM To compare the healing effects of vonoprazan and lansoprazole on gastric ulcers induced by endoscopic submucosal dissection(ESD).METHODS Data were obtained from a total of 26 patients.Fourteen patients were random...AIM To compare the healing effects of vonoprazan and lansoprazole on gastric ulcers induced by endoscopic submucosal dissection(ESD).METHODS Data were obtained from a total of 26 patients.Fourteen patients were randomized to the vonoprazan group and 12 were randomized to the lansoprazole group.Patients were administered either 20 mg vonoprazan or 30 mg lansoprazole per day after ESD.Endoscopic images just after ESD,on day 8,and on day 28 were used for the evaluation of the shrinking rate of ESD ulcers.The shrinking rates and the incidence of delayed bleeding were compared between the 2 groups.RESULTS The shrinking rates of ESD ulcers on day 8 [vonoprazangroup: 61.8%(range: 24.0%-91.1%),lansoprazole group: 71.3%(range: 25.2%-88.6%)] and on day 28 [vonoprazan group: 95.3%(range: 76.2%-100%),lansoprazole group: 97.2%(range: 81.1%-99.8%)] were not statistically different between the 2 groups.On day 28,most of the ulcers in both groups healed to more than 90%,whereas 3 of 14(21.4%) in the vonoprazan group and 1 of 12(8.3%) in the lansoprazole group had delayed ulcer healing,which was not statistically different(P = 0.356).The frequency of delayed bleeding was 0 in the both groups.Taken together,there were no significant differences between the two drug groups.CONCLUSION Our study indicates that vonoprazan is potent for the management of ESD ulcers although lansoprazole is also sufficient and cost-effective.展开更多
The study focused on the application of high-resolution mass spectrometry for the identification of impurities in pharmaceutical small molecules. A high-performance liquid chromatography (HPLC) coupled high resolution...The study focused on the application of high-resolution mass spectrometry for the identification of impurities in pharmaceutical small molecules. A high-performance liquid chromatography (HPLC) coupled high resolution mass spectrometer (HRMS) was used for identification of oxidative degradation impurities (DIs) of lansoprazole. The utilization of HRMS facilitates to determine the accurate mass of impurities and their fragment/product ions. A fast mass spectrometer (MS) compatible reverse phase chromatography method was used to investigate the oxidative stressed impurities. HPLC column;C18 (50 × 4.6 mm, 3.5 μm) was used with gradient elution. Spectral data acquired using information dependent acquisition (IDA) with real time dynamic background subtraction algorithm (DBS). Three oxidative impurities: DI-I (m/z 386.0781), DI-II (m/z 402.0734) and DI-III (m/z 386.0785), was observed during this study;interpretation of high resolution spectral data of all three impurities was carried out;elemental composition and molecular structure was proposed for major fragments. In this study mass error was found ≤7.7 parts per million (ppm).展开更多
A chromatographic and aspectrophotometric methods for the quantitative determination of lansoprazole in pharmaceutical combinations and human plasma were developed. The analytical parameters were studied according to ...A chromatographic and aspectrophotometric methods for the quantitative determination of lansoprazole in pharmaceutical combinations and human plasma were developed. The analytical parameters were studied according to International Conference on Harmonization guidelines. The Flow Injection Analysis (FIA) method is based on the oxidation of lansoprazole by a known excess of N-bromosuccinimide (NBS) in an acidic medium, followed by a reaction of excess oxidant with chloranilic acid (CAA) to bleach its purple color. The separation was carried out using RP-C18 column with a mobile phase composed of ACN: TEA: phosphate buffer (60: 0.2: 39.8 v/v) adjusted to pH = 4.展开更多
Lansoprazole degradation is accelerated in both acidic and basic medium in water. The present investigation deals with the hydrolytic degradation of Lansoprazole. Acidic medium degradation show all known impurities an...Lansoprazole degradation is accelerated in both acidic and basic medium in water. The present investigation deals with the hydrolytic degradation of Lansoprazole. Acidic medium degradation show all known impurities and degradation products whereas basic degradation studies show new impurity which has higher molecular weight than Lansoprazole. New impurity was identified, isolated using mass based auto purification system and characterised by 1H NMR, 13C NMR, HMBC, HSQC, NOE, COSY and HRMS experiments. Isolated impurity was showing molecular weight of 467.10, molecular formula of C23H16F3N5OS and its name is 7-(3-Methyl-4-(2,2,2-trifluoroethoxy) pyridin-2-yl)-7H-benzo[4,5]imidazo[2,1-b]benzo[4,5]imidazo[2,1-d][1,3,5]thiadiazine.展开更多
An optimized formulation of capsules containing Lansoprazole enteric-coated pellets using D-Optimal design with a polynomial statistical model were prepared by using Eudragit?L100 as an enteric coated polymer to provi...An optimized formulation of capsules containing Lansoprazole enteric-coated pellets using D-Optimal design with a polynomial statistical model were prepared by using Eudragit?L100 as an enteric coated polymer to provide resistance to simulated gastric acid dissolution in buffer media. D-Optimal experimental design was used to determine the optimal level for three coating layers that were applied to formulate the enteric-coated pellets including a drug loading layer, a sub-coating, and an outer enteric coating. Dissolution studies were performed on the prepared Lansoprazole capsules. Less than 5 percent of Lansoprazole was released in 60 minutes in an acidic dissolution medium (pH 1.2) and greater than 90 percent of active ingredient was released in the next 60 minutes in a buffer dissolution medium (pH 6.8). The Lansoprazole capsules were stable with no observable change in physico-chemical properties in accelerated and normal storage conditions for 6 and 18 months, respectively. The pharmacokinetic parameters Cmax, Tmax, AUC0-t, and AUC0-∞ were determined after administration of the D-Optimal design optimized capsules of LPZ to healthy beagle dogs and were statistically compared to Gastevin? capsules as a reference (KRKA, Slovenia) using the non-compartmental method with the aid of WinNonlin 5.2 software. The analysis of variance showed that the two formulations did not demonstrate bioequivalence using a 90% confidence interval range (80% - 120%) of Cmax, AUC0-t, and AUC0-∞. No significant difference in Tmax was found at the 0.95 significance level using the Wilcoxon signed-rank test. D-Optimal Experimental Design provided definitive direction for an optimal formulation of capsules containing enteric-coated pellets of lansoprazole loaded within the coating of pellets that provided similar bioequivalence to Gastevin.展开更多
The gastroesophageal reflux and/or peptic ulcer diseases are clinical conditions that occur usually accompanied of symptomatic pain. Lansoprazole, a proton pump inhibitor class drug is widely used in clinical practice...The gastroesophageal reflux and/or peptic ulcer diseases are clinical conditions that occur usually accompanied of symptomatic pain. Lansoprazole, a proton pump inhibitor class drug is widely used in clinical practice for treatment of these diseases. However, its efficacy can be improved by combining with spasmolytic and/or visceral analgesic such as hyoscine butylbromide. Since hyoscine butylbromide is barely absorbed and exerts some local effects at gastrointestinal tract which may modify the absorption of lansoprazole, it is important to establish if there is a pharmacokinetic interaction after the oral concomitant administration of both drugs. For this objective, twenty-five subjects received under a crossover design an oral administration of lansoprazole (15 mg) plus placebo or a fixed-dose combination with hyoscine butiylbromide (15 mg + 10 mg, respectively). Plasma samples were obtained at different times during 10 hours. Lansoprazole plasma concentrations were determined by a high performance liquid chromatography method coupled to tandem mass spectrometry. Fixed-dose combination was well tolerated. Lansoprazole pharmacokinetic parameters were: Cmax 621.81 ± 212.79 and 450.38 ± 192.14 ng/mL;AUC<sub>0</sub><sub>-</sub><sub>t</sub> 1941.36 ± 845.57 and 1454.66 ± 757.28 ng·h/mL;tmax 2.83 ± 0.99 and 3.40 ± 1.82h;t1/2 1.35 ± 0.39 and 1.45 ± 0.51 h, for alone and combined fixed-dose formulation, respectively. Pharmacokinetic parameters were compared by analysis of variance and ratios of AUC<sub>0</sub><sub>-</sub><sub>t</sub>, Cmax and 90% confidence intervals obtained. Since confidence intervals exceed the 80% - 125% limits for these parameters, we conclude that there is a significantly pharmacokinetic interaction of lansoprazole when it is administered concomitantly with hyoscine butylbromide.展开更多
Drug repurposing offers an efficient approach to therapeutic development.In this study,our bioinformatic analysis first predicted an association between obesity and lansoprazole(LPZ),a commonly prescribed drug for gas...Drug repurposing offers an efficient approach to therapeutic development.In this study,our bioinformatic analysis first predicted an association between obesity and lansoprazole(LPZ),a commonly prescribed drug for gastrointestinal ulcers.We went on to show that LPZ treatment increased energy expenditure and alleviated the high-fat diet-induced obesity,insulin resistance,and hepatic stea-tosis in mice.Treatment with LPZ elicited thermogenic gene expression and mitochondrial respiration in primary adipocytes,and induced cold tolerance in cold-exposed mice,suggesting the activity of LPZ in promoting adipose thermogenesis and energy metabolism.Mechanistically,LPZ is an efficient inhibitor of adipose phosphocholine phosphatase 1(PHOSPHOI)and produces metabolic benefits in a PHOS-PHO1-dependent manner.Our results suggested that LPZ may stimulate adipose thermogenesis by inhi-biting the conversion of 2-arachidonoylglycerol-lysophosphatidic acid(2-AG-LPA)to 2-arachidonoylglycerol(2-AG)and reduce the activity of the thermogenic-suppressive cannabinoid recep-tor signaling.In summary,we have uncovered a novel therapeutic indication and mechanism of LPZ in managing obesity and its related metabolic syndrome,and identified a potential metabolic basis by which LPZ improves energy metabolism.展开更多
BACKGROUND The role of primary-level medical pharmacists in medical institutions in China is limited;therefore,it is necessary to explore the role of pharmacists in the process of drug treatment.CASE SUMMARY A Chinese...BACKGROUND The role of primary-level medical pharmacists in medical institutions in China is limited;therefore,it is necessary to explore the role of pharmacists in the process of drug treatment.CASE SUMMARY A Chinese pharmacist participated in the complete treatment of a patient with a duodenal ulcer.The rationale for drug treatment was evaluated,and adjustments were made to the antacid and anti-infective regimen,as well as the dose and frequency of administration.Body temperature,routine blood examination,and adverse drug reactions were strictly monitored.During treatment,the pharmacist recommended anti-infective therapy with ampicillin-sulbactam,which effectively controlled the infection.Additionally,the pharmacist suggested changing famotidine to lansoprazole for acid suppression and gastroprotective treatment,combined with Chinese patent medicine such as Kangfuxin Liquid.This is the first case report of a pharmacist in primary-level medical institutions adjusting drug use for patients with duodenal ulcer and pulmonary infection.CONCLUSION A pharmacist participated in the treatment process,provided individualized medication adjustment,and achieved good clinical results.展开更多
In this study,a specific and rapid high-performance liquid chromatography(HPLC)method has been developed and validated for the simultaneous determination of amoxicillin,lansoprazole,and levofloxacin in pharmaceuticals...In this study,a specific and rapid high-performance liquid chromatography(HPLC)method has been developed and validated for the simultaneous determination of amoxicillin,lansoprazole,and levofloxacin in pharmaceuticals.Paracetamol was used as internal standard(IS)in the measurements.UV-Vis absorption spectra of the analytes and the IS were taken for the determination of suitable absorption wavelength of UV-Vis detector(diode array detector,DAD)in the HPLC instrument.A reverse-phase C18 column was used in the separation and determination of amoxicillin,lansoprazole,and levofloxacin together with the IS.The pharmaceutical analytes were quantified by the UV-Vis diode array detector in the HPLC using MeOH-0.01 M CH_(3)COONH_(4)(70:30)as the mobile phase.The linear calibration curves of them were measured in the ranges of 15-40 mg/L,2.5-15.0 mg/L,and 7.5-20.0 mg/L for amoxicillin,lansoprazole,and levofloxacin,respectively.Excellent calibration correlations(R^(2):0.9942,0.9997,and 0.9974)were obtained.The percentage recoveries of the amoxicillin,lan-soprazole,and levofloxacin in commercial pharmaceuticals were obtained as 105.5%,98.57%,and 102.5%,respectively.The results showed that amoxicillin,lansoprazole,and levofloxacin together with paracetamol IS could be separated and determined simultaneously with low LOD and LOQ values using the proposed HPLC method.展开更多
Clopidogrel is a widely used antiplatelet agent for the secondary prevention of cardiovascular events in patients with stable coronary heart disease, acute coronary syndromes and ischemic stroke. Even though clopidogr...Clopidogrel is a widely used antiplatelet agent for the secondary prevention of cardiovascular events in patients with stable coronary heart disease, acute coronary syndromes and ischemic stroke. Even though clopidogrel is safer than aspirin in terms of risk for gastrointestinal(GI) bleeding, the elderly, and patients with a history of prior GI bleeding, with Helicobacter pylori infection or those who are also treated with aspirin, anticoagulants, corticosteroids or nonsteroidal antiinflammatory drugs are at high risk for GI complications when treated with clopidogrel. Accordingly, proton pump inhibitors are frequently administered in combination with clopidogrel to reduce the risk for GI bleeding. Nevertheless, pharmacodynamic studies suggest that omeprazole might attenuate the antiplatelet effect of clopidogrel. However, in observational studies, this interaction does not appear to translate into increased cardiovascular risk in patients treated with this combination. Moreover, in the only randomized, double-blind study that assessed the cardiovascular implications of combining clopidogrel and omeprazole, patients treated with clopidogrel/omeprazole combination had reduced risk for GI events and similar risk for cardiovascular events than patients treated with clopidogrel and placebo. However, the premature interruption of the study and the lack of power analysis in terms of the cardiovascular endpoint do not allow definite conclusions regarding the cardiovascular safety of clopidogrel/omeprazole combination. Other proton pump inhibitors do not appear to interact with clopidogrel. Nevertheless, given the limitations of existing observational and interventional studies, the decision to administer proton pump inhibitors to patients treated with clopidogrel should be individualized based on the patient's bleeding and cardiovascular risk.展开更多
注射用兰索拉唑（国药准字H20100066号，悦康药业集团有限公司生产，30mg／支），为白色至类白色冻干块状物或粉末。英文名称：Lansoprazole for Injection，适用于治疗口服疗法不适用的伴有出血的十二指肠溃疡。盐酸左氧氟沙星氯化钠...注射用兰索拉唑（国药准字H20100066号，悦康药业集团有限公司生产，30mg／支），为白色至类白色冻干块状物或粉末。英文名称：Lansoprazole for Injection，适用于治疗口服疗法不适用的伴有出血的十二指肠溃疡。盐酸左氧氟沙星氯化钠注射液，为淡黄绿色或黄绿色澄明液体，英文名称Levofloxacin Hydrochloride and Sodium Chloride Injection，用于治疗或预防已证明或高度怀疑由敏感细菌引起的感染。在临床使用过程中，笔者发现注射用兰索拉唑与盐酸左氧氟沙星氯化钠注射液在序贯输注时两者存在配伍禁忌。查阅药物说明书并检索了配伍禁忌表，未查到上述药物配伍禁忌说明，为了避免给患者造成伤害及药物浪费，对上述药物进行了实验观察，现报告如下。展开更多
Cholesterol is an important precursor of many endogenous molecules.Disruption of cholesterol homeostasis can cause many pathological changes,leading to liver and cardiovascular diseases.CYP1A is widely involved in cho...Cholesterol is an important precursor of many endogenous molecules.Disruption of cholesterol homeostasis can cause many pathological changes,leading to liver and cardiovascular diseases.CYP1A is widely involved in cholesterol metabolic network,but its exact function has not been fully elucidated.Here,we aim to explore how CYP1A regulates cholesterol homeostasis.Our data showed that CYP1A1/2 knockout(KO)rats presented cholesterol deposition in blood and liver.The serum levels of low-density lipoprotein cholesterol,high-density lipoprotein cholesterol and total cholesterol were significantly increased in KO rats.Further studies found that the lipogenesis pathway(LXRa-SREBP1-SCD1)of KO rats was activated,and the key protein of cholesterol ester hydrolysis(CES1)was inhibited.Importantly,lansoprazole can significantly alleviate rat hepatic lipid deposition in hypercholesterolemia models by inducing CYP1A.Our findings reveal the role of CYP1A as a potential regulator of cholesterol homeostasis and provide a new perspective for the treatment of hypercholesterolemia.展开更多
文摘AIM To compare vonoprazan 10 and 20 mg vs lansoprazole 15 mg as maintenance therapy in healed erosive esophagitis(EE).METHODS A total of 607 patients aged ≥ 20 years, with endoscopically-confirmed healed EE following 8 wk of treatment with vonoprazan 20 mg once daily, were randomized 1:1:1 to receive lansoprazole 15 mg(n = 201), vonoprazan 10 mg(n = 202), or vonoprazan 20 mg(n = 204), once daily. The primary endpoint of the study was the rate of endoscopically-confirmed EE recurrence during a 24-wk maintenance period. The secondary endpoint was the EE recurrence rate at Week 12 during maintenance treatment. Additional efficacy endpoints included the incidence of heartburn and acid reflux, and the EE healing rate 4 wk after the initiation of maintenance treatment. Safety endpoints comprised adverse events(AEs), vital signs, electrocardiogram findings, clinical laboratory results, serum gastrin and pepsinogen Ⅰ/Ⅱ levels, and gastric mucosa histopathology results.RESULTS Rates of EE recurrence during the 24-wk maintenance period were 16.8%, 5.1%, and 2.0% with lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg, respectively. Vonoprazan was shown to be non-inferior to lansoprazole 15 mg(P < 0.0001 for both doses). In a post-hoc analysis, EE recurrence at Week 24 was significantly reduced with vonoprazan at both the 10 mg and the 20 mg dose vs lansoprazole 15 mg(5.1% vs 16.8%, P = 0.0002, and 2.0% vs 16.8%, P < 0.0001, respectively); by contrast, the EE recurrence rate did not differ significantly between the two doses of vonoprazan(P = 0.1090). The safety profiles of vonoprazan 10 and 20 mg were similar to that of lansoprazole 15 mg in patients with healed EE. Treatment-related AEs were reported in 11.4%, 10.4%, and 10.3% of patients in the lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg arms, respectively.CONCLUSION Our findings confirm the non-inferiority of vonoprazan 10 and 20 mg to lansoprazole 15 mg as maintenance therapy for patients with healed EE.
文摘AIM To compare the healing effects of vonoprazan and lansoprazole on gastric ulcers induced by endoscopic submucosal dissection(ESD).METHODS Data were obtained from a total of 26 patients.Fourteen patients were randomized to the vonoprazan group and 12 were randomized to the lansoprazole group.Patients were administered either 20 mg vonoprazan or 30 mg lansoprazole per day after ESD.Endoscopic images just after ESD,on day 8,and on day 28 were used for the evaluation of the shrinking rate of ESD ulcers.The shrinking rates and the incidence of delayed bleeding were compared between the 2 groups.RESULTS The shrinking rates of ESD ulcers on day 8 [vonoprazangroup: 61.8%(range: 24.0%-91.1%),lansoprazole group: 71.3%(range: 25.2%-88.6%)] and on day 28 [vonoprazan group: 95.3%(range: 76.2%-100%),lansoprazole group: 97.2%(range: 81.1%-99.8%)] were not statistically different between the 2 groups.On day 28,most of the ulcers in both groups healed to more than 90%,whereas 3 of 14(21.4%) in the vonoprazan group and 1 of 12(8.3%) in the lansoprazole group had delayed ulcer healing,which was not statistically different(P = 0.356).The frequency of delayed bleeding was 0 in the both groups.Taken together,there were no significant differences between the two drug groups.CONCLUSION Our study indicates that vonoprazan is potent for the management of ESD ulcers although lansoprazole is also sufficient and cost-effective.
文摘The study focused on the application of high-resolution mass spectrometry for the identification of impurities in pharmaceutical small molecules. A high-performance liquid chromatography (HPLC) coupled high resolution mass spectrometer (HRMS) was used for identification of oxidative degradation impurities (DIs) of lansoprazole. The utilization of HRMS facilitates to determine the accurate mass of impurities and their fragment/product ions. A fast mass spectrometer (MS) compatible reverse phase chromatography method was used to investigate the oxidative stressed impurities. HPLC column;C18 (50 × 4.6 mm, 3.5 μm) was used with gradient elution. Spectral data acquired using information dependent acquisition (IDA) with real time dynamic background subtraction algorithm (DBS). Three oxidative impurities: DI-I (m/z 386.0781), DI-II (m/z 402.0734) and DI-III (m/z 386.0785), was observed during this study;interpretation of high resolution spectral data of all three impurities was carried out;elemental composition and molecular structure was proposed for major fragments. In this study mass error was found ≤7.7 parts per million (ppm).
文摘A chromatographic and aspectrophotometric methods for the quantitative determination of lansoprazole in pharmaceutical combinations and human plasma were developed. The analytical parameters were studied according to International Conference on Harmonization guidelines. The Flow Injection Analysis (FIA) method is based on the oxidation of lansoprazole by a known excess of N-bromosuccinimide (NBS) in an acidic medium, followed by a reaction of excess oxidant with chloranilic acid (CAA) to bleach its purple color. The separation was carried out using RP-C18 column with a mobile phase composed of ACN: TEA: phosphate buffer (60: 0.2: 39.8 v/v) adjusted to pH = 4.
文摘Lansoprazole degradation is accelerated in both acidic and basic medium in water. The present investigation deals with the hydrolytic degradation of Lansoprazole. Acidic medium degradation show all known impurities and degradation products whereas basic degradation studies show new impurity which has higher molecular weight than Lansoprazole. New impurity was identified, isolated using mass based auto purification system and characterised by 1H NMR, 13C NMR, HMBC, HSQC, NOE, COSY and HRMS experiments. Isolated impurity was showing molecular weight of 467.10, molecular formula of C23H16F3N5OS and its name is 7-(3-Methyl-4-(2,2,2-trifluoroethoxy) pyridin-2-yl)-7H-benzo[4,5]imidazo[2,1-b]benzo[4,5]imidazo[2,1-d][1,3,5]thiadiazine.
文摘An optimized formulation of capsules containing Lansoprazole enteric-coated pellets using D-Optimal design with a polynomial statistical model were prepared by using Eudragit?L100 as an enteric coated polymer to provide resistance to simulated gastric acid dissolution in buffer media. D-Optimal experimental design was used to determine the optimal level for three coating layers that were applied to formulate the enteric-coated pellets including a drug loading layer, a sub-coating, and an outer enteric coating. Dissolution studies were performed on the prepared Lansoprazole capsules. Less than 5 percent of Lansoprazole was released in 60 minutes in an acidic dissolution medium (pH 1.2) and greater than 90 percent of active ingredient was released in the next 60 minutes in a buffer dissolution medium (pH 6.8). The Lansoprazole capsules were stable with no observable change in physico-chemical properties in accelerated and normal storage conditions for 6 and 18 months, respectively. The pharmacokinetic parameters Cmax, Tmax, AUC0-t, and AUC0-∞ were determined after administration of the D-Optimal design optimized capsules of LPZ to healthy beagle dogs and were statistically compared to Gastevin? capsules as a reference (KRKA, Slovenia) using the non-compartmental method with the aid of WinNonlin 5.2 software. The analysis of variance showed that the two formulations did not demonstrate bioequivalence using a 90% confidence interval range (80% - 120%) of Cmax, AUC0-t, and AUC0-∞. No significant difference in Tmax was found at the 0.95 significance level using the Wilcoxon signed-rank test. D-Optimal Experimental Design provided definitive direction for an optimal formulation of capsules containing enteric-coated pellets of lansoprazole loaded within the coating of pellets that provided similar bioequivalence to Gastevin.
文摘The gastroesophageal reflux and/or peptic ulcer diseases are clinical conditions that occur usually accompanied of symptomatic pain. Lansoprazole, a proton pump inhibitor class drug is widely used in clinical practice for treatment of these diseases. However, its efficacy can be improved by combining with spasmolytic and/or visceral analgesic such as hyoscine butylbromide. Since hyoscine butylbromide is barely absorbed and exerts some local effects at gastrointestinal tract which may modify the absorption of lansoprazole, it is important to establish if there is a pharmacokinetic interaction after the oral concomitant administration of both drugs. For this objective, twenty-five subjects received under a crossover design an oral administration of lansoprazole (15 mg) plus placebo or a fixed-dose combination with hyoscine butiylbromide (15 mg + 10 mg, respectively). Plasma samples were obtained at different times during 10 hours. Lansoprazole plasma concentrations were determined by a high performance liquid chromatography method coupled to tandem mass spectrometry. Fixed-dose combination was well tolerated. Lansoprazole pharmacokinetic parameters were: Cmax 621.81 ± 212.79 and 450.38 ± 192.14 ng/mL;AUC<sub>0</sub><sub>-</sub><sub>t</sub> 1941.36 ± 845.57 and 1454.66 ± 757.28 ng·h/mL;tmax 2.83 ± 0.99 and 3.40 ± 1.82h;t1/2 1.35 ± 0.39 and 1.45 ± 0.51 h, for alone and combined fixed-dose formulation, respectively. Pharmacokinetic parameters were compared by analysis of variance and ratios of AUC<sub>0</sub><sub>-</sub><sub>t</sub>, Cmax and 90% confidence intervals obtained. Since confidence intervals exceed the 80% - 125% limits for these parameters, we conclude that there is a significantly pharmacokinetic interaction of lansoprazole when it is administered concomitantly with hyoscine butylbromide.
基金This work was supported by the Beijing Municipal Natural Science Foundation Grant 7212148(to Mengxi Jiang,China)the National Natural Science Foundation of China Grant 82000807(to Mengxi Jiang,China)the Beijing Municipal Education Commission Grant KM202110025023(to Mengxi Jiang,China).
文摘Drug repurposing offers an efficient approach to therapeutic development.In this study,our bioinformatic analysis first predicted an association between obesity and lansoprazole(LPZ),a commonly prescribed drug for gastrointestinal ulcers.We went on to show that LPZ treatment increased energy expenditure and alleviated the high-fat diet-induced obesity,insulin resistance,and hepatic stea-tosis in mice.Treatment with LPZ elicited thermogenic gene expression and mitochondrial respiration in primary adipocytes,and induced cold tolerance in cold-exposed mice,suggesting the activity of LPZ in promoting adipose thermogenesis and energy metabolism.Mechanistically,LPZ is an efficient inhibitor of adipose phosphocholine phosphatase 1(PHOSPHOI)and produces metabolic benefits in a PHOS-PHO1-dependent manner.Our results suggested that LPZ may stimulate adipose thermogenesis by inhi-biting the conversion of 2-arachidonoylglycerol-lysophosphatidic acid(2-AG-LPA)to 2-arachidonoylglycerol(2-AG)and reduce the activity of the thermogenic-suppressive cannabinoid recep-tor signaling.In summary,we have uncovered a novel therapeutic indication and mechanism of LPZ in managing obesity and its related metabolic syndrome,and identified a potential metabolic basis by which LPZ improves energy metabolism.
文摘BACKGROUND The role of primary-level medical pharmacists in medical institutions in China is limited;therefore,it is necessary to explore the role of pharmacists in the process of drug treatment.CASE SUMMARY A Chinese pharmacist participated in the complete treatment of a patient with a duodenal ulcer.The rationale for drug treatment was evaluated,and adjustments were made to the antacid and anti-infective regimen,as well as the dose and frequency of administration.Body temperature,routine blood examination,and adverse drug reactions were strictly monitored.During treatment,the pharmacist recommended anti-infective therapy with ampicillin-sulbactam,which effectively controlled the infection.Additionally,the pharmacist suggested changing famotidine to lansoprazole for acid suppression and gastroprotective treatment,combined with Chinese patent medicine such as Kangfuxin Liquid.This is the first case report of a pharmacist in primary-level medical institutions adjusting drug use for patients with duodenal ulcer and pulmonary infection.CONCLUSION A pharmacist participated in the treatment process,provided individualized medication adjustment,and achieved good clinical results.
文摘In this study,a specific and rapid high-performance liquid chromatography(HPLC)method has been developed and validated for the simultaneous determination of amoxicillin,lansoprazole,and levofloxacin in pharmaceuticals.Paracetamol was used as internal standard(IS)in the measurements.UV-Vis absorption spectra of the analytes and the IS were taken for the determination of suitable absorption wavelength of UV-Vis detector(diode array detector,DAD)in the HPLC instrument.A reverse-phase C18 column was used in the separation and determination of amoxicillin,lansoprazole,and levofloxacin together with the IS.The pharmaceutical analytes were quantified by the UV-Vis diode array detector in the HPLC using MeOH-0.01 M CH_(3)COONH_(4)(70:30)as the mobile phase.The linear calibration curves of them were measured in the ranges of 15-40 mg/L,2.5-15.0 mg/L,and 7.5-20.0 mg/L for amoxicillin,lansoprazole,and levofloxacin,respectively.Excellent calibration correlations(R^(2):0.9942,0.9997,and 0.9974)were obtained.The percentage recoveries of the amoxicillin,lan-soprazole,and levofloxacin in commercial pharmaceuticals were obtained as 105.5%,98.57%,and 102.5%,respectively.The results showed that amoxicillin,lansoprazole,and levofloxacin together with paracetamol IS could be separated and determined simultaneously with low LOD and LOQ values using the proposed HPLC method.
文摘Clopidogrel is a widely used antiplatelet agent for the secondary prevention of cardiovascular events in patients with stable coronary heart disease, acute coronary syndromes and ischemic stroke. Even though clopidogrel is safer than aspirin in terms of risk for gastrointestinal(GI) bleeding, the elderly, and patients with a history of prior GI bleeding, with Helicobacter pylori infection or those who are also treated with aspirin, anticoagulants, corticosteroids or nonsteroidal antiinflammatory drugs are at high risk for GI complications when treated with clopidogrel. Accordingly, proton pump inhibitors are frequently administered in combination with clopidogrel to reduce the risk for GI bleeding. Nevertheless, pharmacodynamic studies suggest that omeprazole might attenuate the antiplatelet effect of clopidogrel. However, in observational studies, this interaction does not appear to translate into increased cardiovascular risk in patients treated with this combination. Moreover, in the only randomized, double-blind study that assessed the cardiovascular implications of combining clopidogrel and omeprazole, patients treated with clopidogrel/omeprazole combination had reduced risk for GI events and similar risk for cardiovascular events than patients treated with clopidogrel and placebo. However, the premature interruption of the study and the lack of power analysis in terms of the cardiovascular endpoint do not allow definite conclusions regarding the cardiovascular safety of clopidogrel/omeprazole combination. Other proton pump inhibitors do not appear to interact with clopidogrel. Nevertheless, given the limitations of existing observational and interventional studies, the decision to administer proton pump inhibitors to patients treated with clopidogrel should be individualized based on the patient's bleeding and cardiovascular risk.
文摘注射用兰索拉唑（国药准字H20100066号，悦康药业集团有限公司生产，30mg／支），为白色至类白色冻干块状物或粉末。英文名称：Lansoprazole for Injection，适用于治疗口服疗法不适用的伴有出血的十二指肠溃疡。盐酸左氧氟沙星氯化钠注射液，为淡黄绿色或黄绿色澄明液体，英文名称Levofloxacin Hydrochloride and Sodium Chloride Injection，用于治疗或预防已证明或高度怀疑由敏感细菌引起的感染。在临床使用过程中，笔者发现注射用兰索拉唑与盐酸左氧氟沙星氯化钠注射液在序贯输注时两者存在配伍禁忌。查阅药物说明书并检索了配伍禁忌表，未查到上述药物配伍禁忌说明，为了避免给患者造成伤害及药物浪费，对上述药物进行了实验观察，现报告如下。
基金supported in whole or part by grants from the National Natural Science Foundation of China(81773808,82274010)the Science and Technology Commission of Shanghai Municipality(18430760400,China)+4 种基金the Jointed PI Program from Shanghai Changning Maternity and Infant Health Hospital(2019CNECNUPI02,China)the Fundamental Research Funds for the Central Universities(China)ECNU Construction Fund of Innovation and Entrepreneurship Laboratory(China)supported from ECNU Multifunctional Platform for Innovation(011,China)the Instruments Sharing Platform of School of Life Sciences,East China Normal University(Shanghai,China)。
文摘Cholesterol is an important precursor of many endogenous molecules.Disruption of cholesterol homeostasis can cause many pathological changes,leading to liver and cardiovascular diseases.CYP1A is widely involved in cholesterol metabolic network,but its exact function has not been fully elucidated.Here,we aim to explore how CYP1A regulates cholesterol homeostasis.Our data showed that CYP1A1/2 knockout(KO)rats presented cholesterol deposition in blood and liver.The serum levels of low-density lipoprotein cholesterol,high-density lipoprotein cholesterol and total cholesterol were significantly increased in KO rats.Further studies found that the lipogenesis pathway(LXRa-SREBP1-SCD1)of KO rats was activated,and the key protein of cholesterol ester hydrolysis(CES1)was inhibited.Importantly,lansoprazole can significantly alleviate rat hepatic lipid deposition in hypercholesterolemia models by inducing CYP1A.Our findings reveal the role of CYP1A as a potential regulator of cholesterol homeostasis and provide a new perspective for the treatment of hypercholesterolemia.
