Objective:Generic drugs provide an opportunity for savings in drug expenditure since they are available at a lower cost and do not affect patients’health.A better understanding of pharmacists’knowledge,attitudes,and...Objective:Generic drugs provide an opportunity for savings in drug expenditure since they are available at a lower cost and do not affect patients’health.A better understanding of pharmacists’knowledge,attitudes,and perception can promote the quality use of generic drugs.The objective of this study was to investigate the knowledge,attitudes,and perception of pharmacists from tertiary hospitals in China regarding generic drugs.Methods:A cross-sectional survey using a postal questionnaire was conducted,which was sent to 200 hospital pharmacists randomly selected from tertiary hospitals in Hubei Province.A total of 125 questionnaires out of 200 were received.Of the respondents,80 were female and 45 were male.Results:The majority of respondents(87.2%)could clearly distinguish between original and generic drugs.Pharmacists agreed that generic drugs were less effective(52.8%)and produced more side effects(52%).Forty-nine respondents thought that generic drug products were not adequately tested.Approximately 78% and 60% of the pharmacists indicated that generic substitution was not feasible for drugs with narrow therapeutic windows and drugs for critical diseases,respectively.Most of them supported the recommendation of generic drugs based on professional judgment.Conclusion:Our study showed that a considerable portion of Chinese hospital pharmacists hold negative perceptions of generic drugs.Interventions to improve pharmacists'knowledge of generic drugs are needed.展开更多
Development of generic drug product by pharmaceutical industry is a scientific and technical approach which is totally different from developing a reference or innovator product. Most of the developing countries focus...Development of generic drug product by pharmaceutical industry is a scientific and technical approach which is totally different from developing a reference or innovator product. Most of the developing countries focus on developing the generic drug products because huge amount of investment is required for innovation and to develop reference product. The generic medicine has to be bioequivalent to the innovator drug and ensure the same biological effect with proper safety and efficacy. Nowadays, the pharmaceutical industries focus on the development of generic product as this does not require that much time and cost compared to the innovator company. But development of generic product is also difficult as it contains the same therapeutic efficacy as innovator. The development approach is based on the target market, i.e. US market, EU market. If a manufacturer targets the US market, then all excipients should be USP grade, analysis should be conducted by USP method or in-house method and stability studies as well. Prior and during the development of generic drug product API selection, dosage form selection, reference product selection and characterization, formulation development, analytical method development, tech transfer or submission batch are prime concern. Then again, bioequivalence study, drug registration procedure and commercialization of the generic product considering regulatory guidance of respective regulatory agencies and the approaches taken by the regulatory agencies for the development of registration of generic medicines are also crucial as well for the development of generic drug product. The aim of this study was to review the entire stage of a generic drug development by a generic pharmaceutical company.展开更多
Objective To study the significance of authorized generic drugs due to the successive relevant documents issued by China’s government in recent years,which clearly stipulated that China should establish a drug patent...Objective To study the significance of authorized generic drugs due to the successive relevant documents issued by China’s government in recent years,which clearly stipulated that China should establish a drug patent linkage system.Methods The authorized generic drugs play an important role in keeping the balance between brandname drugs and generic drugs in the US.Therefore,this system was investigated,focusing on its difference from independent generics,marketing procedures,application in patent litigation and legitimacy analysis through case evidence.This analogy analysis could provide a reference for the research of authorized generic drug systems in China.Results and Conclusion As an important factor affecting the balance between brand-name drugs and generic drugs,authorized generic drugs should be comprehensively analyzed and discussed,and a suitable system for China’s national conditions should be established by referring to the experiences of the US.展开更多
Objective To study the impact of consistency evaluation policy on pharmaceutical enterprises from four aspects:reference preparations,evaluation methods,input costs,and market competitions,and government incentives fo...Objective To study the impact of consistency evaluation policy on pharmaceutical enterprises from four aspects:reference preparations,evaluation methods,input costs,and market competitions,and government incentives for generic drug manufacturers,so as to put forward relevant suggestions.Methods Literature research method and statistical analysis method were used to provide data support for paper writing,making suggestions,and enhancing the predictability of policy.Results and Conclusion Some pharmaceutical enterprises faced difficulties in obtaining reference preparations,high input costs for exploring evaluation methods,and greater market competition.Consistency evaluation is a key measure to comprehensively improve the quality and efficacy of generic drugs.However,difficulties in obtaining reference preparations,high input costs and complex evaluation methods all affect the enthusiasm of companies.Therefore,national and local regulatory agencies have issued some supporting policies,which should be improved to assist enterprises in conducting consistency evaluations.展开更多
Recently,generic drug products have played an increasingly important role in the health care system globally,especially in the developing world,as they provide for an effective and more affordable alternative for heal...Recently,generic drug products have played an increasingly important role in the health care system globally,especially in the developing world,as they provide for an effective and more affordable alternative for healthcare professionals.Generic drug products are proven therapeutically equivalent to the corresponding innovator’s product,and hence can be substituted in clinical practice.The objective of generic drug development is to develop a stable and bioequivalent generic drug product with desirable properties in a timely manner.This presentation is intended to summarize three important sequential stages essential for successful generic drug development based on a regulatory experience in reviewing and evaluating the Pharmaceutical Development Section(P2)of the ASEAN Common Technical Dossier(ACTD)of generic drug product applications submitted to the Food and Drug Administration,Thailand[1,2].展开更多
The key events in the development of the US generic drug industry after the Hatch-Waxman Act of 1984 are systematically reviewed,including the process of approval for generic drugs,bioequivalence issues including“swi...The key events in the development of the US generic drug industry after the Hatch-Waxman Act of 1984 are systematically reviewed,including the process of approval for generic drugs,bioequivalence issues including“switchability”,bioequivalence for complicated dosage forms,patent extension,generic drug safety,generic substitution and low-cost generics.The backlog in generic review,generic drug user fees,and“quality by design”for generic drugs is also discussed.The evolution of the US generic drug industry after the Hatch-Waxman Act in 1984 has afforded several lessons of great benefit to other countries wishing to establish or re-establish a domestic generic drug industry.展开更多
Veterinary drugs are substances(including pharmaceutical feed additives)used to prevent,treat,and diagnose diseases or regulate the physiological functions of animals.Veterinary drug poisoning in humans is relatively ...Veterinary drugs are substances(including pharmaceutical feed additives)used to prevent,treat,and diagnose diseases or regulate the physiological functions of animals.Veterinary drug poisoning in humans is relatively rare both in China and the rest of the world.Here,we report a case of death from veterinary drug poisoning from avermectin-closantel.Avermectin-closantel is a broad-spectrum antiparasitic drug,which has high efficacy against a variety of trematodes and nematodes.展开更多
Tauopathies,diseases characterized by neuropathological aggregates of tau including Alzheimer's disease and subtypes of fro ntotemporal dementia,make up the vast majority of dementia cases.Although there have been...Tauopathies,diseases characterized by neuropathological aggregates of tau including Alzheimer's disease and subtypes of fro ntotemporal dementia,make up the vast majority of dementia cases.Although there have been recent developments in tauopathy biomarkers and disease-modifying treatments,ongoing progress is required to ensure these are effective,economical,and accessible for the globally ageing population.As such,continued identification of new potential drug targets and biomarkers is critical."Big data"studies,such as proteomics,can generate information on thousands of possible new targets for dementia diagnostics and therapeutics,but currently remain underutilized due to the lack of a clear process by which targets are selected for future drug development.In this review,we discuss current tauopathy biomarkers and therapeutics,and highlight areas in need of improvement,particularly when addressing the needs of frail,comorbid and cognitively impaired populations.We highlight biomarkers which have been developed from proteomic data,and outline possible future directions in this field.We propose new criteria by which potential targets in proteomics studies can be objectively ranked as favorable for drug development,and demonstrate its application to our group's recent tau interactome dataset as an example.展开更多
Traditional tumor models do not tend to accurately simulate tumor growth in vitro or enable personalized treatment and are particularly unable to discover more beneficial targeted drugs.To address this,this study desc...Traditional tumor models do not tend to accurately simulate tumor growth in vitro or enable personalized treatment and are particularly unable to discover more beneficial targeted drugs.To address this,this study describes the use of threedimensional(3D)bioprinting technology to construct a 3D model with human hepatocarcinoma SMMC-7721 cells(3DP-7721)by combining gelatin methacrylate(GelMA)and poly(ethylene oxide)(PEO)as two immiscible aqueous phases to form a bioink and innovatively applying fluorescent carbon quantum dots for long-term tracking of cells.The GelMA(10%,mass fraction)and PEO(1.6%,mass fraction)hydrogel with 3:1 volume ratio offered distinct pore-forming characteristics,satisfactorymechanical properties,and biocompatibility for the creation of the 3DP-7721 model.Immunofluorescence analysis and quantitative real-time fluorescence polymerase chain reaction(PCR)were used to evaluate the biological properties of the model.Compared with the two-dimensional culture cell model(2D-7721)and the 3D mixed culture cell model(3DM-7721),3DP-7721 significantly improved the proliferation of cells and expression of tumor-related proteins and genes.Moreover,we evaluated the differences between the three culture models and the effectiveness of antitumor drugs in the three models and discovered that the efficacy of antitumor drugs varied because of significant differences in resistance proteins and genes between the three models.In addition,the comparison of tumor formation in the three models found that the cells cultured by the 3DP-7721 model had strong tumorigenicity in nude mice.Immunohistochemical evaluation of the levels of biochemical indicators related to the formation of solid tumors showed that the 3DP-7721 model group exhibited pathological characteristics of malignant tumors,the generated solid tumors were similar to actual tumors,and the deterioration was higher.This research therefore acts as a foundation for the application of 3DP-7721 models in drug development research.展开更多
Multiple sclerosis(MS)is an autoimmune disorder of the central nervous system(CNS)and is primarily characterized by immune cell infiltration leading to relapses followed by remission phases and a disease course turnin...Multiple sclerosis(MS)is an autoimmune disorder of the central nervous system(CNS)and is primarily characterized by immune cell infiltration leading to relapses followed by remission phases and a disease course turning progressive over time with neurodegenerative processes taking over(Amin and Hersh,2023).Of note,beyond relapse-associated worsening early in disease progression independent of relapse activity may arise independently of relapse activity and can occur in all phenotypes.Autoimmune-mediated damage of myelin sheaths and the subsequent loss of mature oligodendrocytes are resulting in impaired axonal integrity,neurodegeneration and accounts for irreversible neuronal damage(Kuhlmann et al.,2023).The current landscape of available disease-modifying therapies comprises mainly immunomodulatory drugs that effectively diminish relapses and slow down progression at the onset form of the disease,namely relapsing MS(RMS).In this regard,a number of drugs have been approved as disease-modifying therapies for MS by US Food and Drug Administration and European Medicines Agencies(Box 1).展开更多
Cancer immunotherapy has emerged as a promising approach in cancer treatment and is considered a major advancement after surgical interventions, radiotherapy, chemotherapy, and targeted therapy. The clinical use of im...Cancer immunotherapy has emerged as a promising approach in cancer treatment and is considered a major advancement after surgical interventions, radiotherapy, chemotherapy, and targeted therapy. The clinical use of immunotherapeutic drugs, particularly antibody-based drugs that target immune checkpoints, has notably increased~1.展开更多
Percutaneous coronary interventions have progressed through the era of plain balloon dilation, bare-metal stent insertion to drug-eluting stent treatment, which has significantly reduced the acute occlusion and resten...Percutaneous coronary interventions have progressed through the era of plain balloon dilation, bare-metal stent insertion to drug-eluting stent treatment, which has significantly reduced the acute occlusion and restenosis rates of target vessels and improved patient prognosis, making drug-eluting stents the mainstream interventional treatment for coronary artery disease. In recent years, drug-coated balloons(DCBs) have become a new treatment strategy for coronary artery disease, and the drugs used in the coating and the coating technology have progressed in the past years. Without permanent implant, a DCB delivers antiproliferative drugs rapidly and uniformly into the vessel wall via the excipient during a single balloon dilation. Many evidence suggests that DCB angioplasty is an effective measure for dealing with in-stent restenosis and de novo lesions in small coronary vessels.As more clinical studies are published, new evidence is emerging for the use of DCB angioplasty in a wide range of coronary diseases, and the indications are expanding internationally. Based on the latest research from China and elsewhere, the Expert Writing Committee of the Chinese Expert Consensus on Clinical Applications of Drug-Coated Balloon has updated the previous DCB consensus after evidence-based discussions and meetings in terms of adequate preparation of in-stent restenosis lesions, expansion of the indications for coronary de novo lesions, and precise guidance of DCB treatment by intravascular imaging and functional evaluation.展开更多
The main aim of antineoplastic treatment is to maximize patient benefit by augmenting the drug accumulation within affected organs and tissues,thus incrementing drug effects and,at the same time,reducing the damage of...The main aim of antineoplastic treatment is to maximize patient benefit by augmenting the drug accumulation within affected organs and tissues,thus incrementing drug effects and,at the same time,reducing the damage of non-involved tissues to cytotoxic agents.Mesenchymal stromal cells(MSC)represent a group of undifferentiated multipotent cells presenting wide self-renewal features and the capacity to differentiate into an assortment of mesenchymal family cells.During the last year,they have been proposed as natural carriers for the selective release of antitumor drugs to malignant cll,s thus optimizing cytotoxic action on cancer cll,while significantly reducing adverse side efect on healthy cells.MSC chemotherapeutic drug loading and delivery is an encouraging new area of cell therapy for several tumors,especially for those with unsatisfactory prognosis and limited treatment options available.Although some experim ental models have been sucesfuly developed,phase I dinical studies are needed to confirm this potential application of cell therapy,in particular in the case of primary and secondary lung cancers.展开更多
Some bacteria have the ability to co-exist, proliferate and survive in a multicellular community, biofilm. Each participating bacteria can form its colonies and encases itself by a self-produced insoluble extracellula...Some bacteria have the ability to co-exist, proliferate and survive in a multicellular community, biofilm. Each participating bacteria can form its colonies and encases itself by a self-produced insoluble extracellular matrix substance (EPS). Microcolonies within biofilm are held together by interactions and bonding of the substances present in the EPS with their separation from the water channels. Similar to insoluble EPS, bacterial microcolonies release soluble exofactors that have direct impacts on the survivability, growth and antibacterial resistivity of other microcolonies made of single- or multi-species bacteria in the same biofilm. How the exofactors of microcolonies of one-type bacteria impact on microcolonies of other-type bacteria is still unclear. We studied about the role of exofactors released from Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa, which are common biofilm-forming pathogenic bacteria. Exofactors facilitate to transform the microenvironment where bacteria can acquire alternative lifestyle with a long survival period and resistivity to certain antimicrobial drugs.展开更多
[Objectives]To establish a new management model for rational use of perioperative antibacterial drugs in surgical departments.[Methods]Based on evidence-based medicine,the department s drug pathway was formulated,and ...[Objectives]To establish a new management model for rational use of perioperative antibacterial drugs in surgical departments.[Methods]Based on evidence-based medicine,the department s drug pathway was formulated,and the new mode of rational drug use control was established by using fine pharmaceutical technology intervention,and the intervention effect was evaluated by the intensity of antibacterial drug use,per capita drug costs and the proportion of drugs.[Results]After adopting drug pathway in departments,the intensity of antibacterial drug use,per capita drug costs and the proportion of drugs decreased significantly,and the effect of rational drug use control was remarkable.[Conclusions]The drug pathway provides a new management and control mode for the rational use of perioperative antibacterial drugs in surgical departments of hospitals.Thus,it is worthy of popularization and application.展开更多
Introduction: The epidemiology of both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among drug users (DUs) is little known in West Africa. The study aimed to assess the prevalence of hepatitis B and ...Introduction: The epidemiology of both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among drug users (DUs) is little known in West Africa. The study aimed to assess the prevalence of hepatitis B and C viruses among drug users in Burkina Faso. Methodology: This was a cross-sectional biological and behavioral survey conducted between June and August 2022, among drug users in Ouagadougou and Bobo Dioulasso, the two main cities of Burkina Faso. A respondent-driven sampling (RDS) was used to recruit drug users. Hepatitis B surface antigen was determined using lateral flow rapid test kits and antibodies to hepatitis C virus in serum determined using an Enzyme-Linked Immunosorbent Assay. Data were entered and analyzed using Stata 17 software. Weighted binary logistic regression was used to identify the associated factors of hepatitis B and C infections and a p-value Results: A total of 323 drug users were recruited with 97.5% males. The mean age was 32.7 years old. The inhaled or smoked mode was the most used by drug users. The adjusted hepatitis B and hepatitis C prevalence among study participants were 11.1% and 2.3% respectively. The marital status (p = 0.001), and the nationality (p = 0.011) were significantly associated with hepatitis B infection. The type of drug used was not significantly associated with hepatitis B infection or hepatitis C infection. Conclusion: The prevalence of HBsAg and anti-HCV antibodies among DUs are comparable to those reported in the general population in Burkina Faso. This result suggests that the main routes of contamination by HBV and HCV among DUs are similar to those in the population, and could be explained by the low use of the injectable route by DUs in Burkina Faso.展开更多
Objective Retinoblastoma(RB)is a prevalent type of eye cancer in youngsters.Prospero homeobox 1(Prox1)is a homeobox transcriptional repressor and downstream target of the proneural gene that is relevant in lymphatic,h...Objective Retinoblastoma(RB)is a prevalent type of eye cancer in youngsters.Prospero homeobox 1(Prox1)is a homeobox transcriptional repressor and downstream target of the proneural gene that is relevant in lymphatic,hepatocyte,pancreatic,heart,lens,retinal,and cancer cells.The goal of this study was to investigate the role of Prox1 in RB cell proliferation and drug resistance,as well as to explore the underlying Notch1 mechanism.Methods Human RB cell lines(SO-RB50 and Y79)and a primary human retinal microvascular endothelial cell line(ACBRI-181)were used in this study.The expression of Prox1 and Notch1 mRNA and protein in RB cells was detected using quantitative real time-polymerase chain reaction(RT-qPCR)and Western blotting.Cell proliferation was assessed after Prox1 overexpression using the Cell Counting Kit-8 and the MTS assay.Drug-resistant cell lines(SO-RB50/vincristine)were generated and treated with Prox1 to investigate the role of Prox1 in drug resistance.We employed pcDNA-Notch1 to overexpress Notch1 to confirm the role of Notch1 in the protective function of Prox1.Finally,a xenograft model was constructed to assess the effect of Prox1 on RB in vivo.Results Prox1 was significantly downregulated in RB cells.Overexpression of Prox1 effectively decreased RB cell growth while increasing the sensitivity of drug-resistant cells to vincristine.Notch1 was involved in Prox1’s regulatory effects.Notch1 was identified as a target gene of Prox1,which was found to be upregulated in RB cells and repressed by increased Prox1 expression.When pcDNA-Notch1 was transfected,the effect of Prox1 overexpression on RB was removed.Furthermore,by downregulating Notch1,Prox1 overexpression slowed tumor development and increased vincristine sensitivity in vivo.Conclusion These data show that Prox1 decreased RB cell proliferation and drug resistance by targeting Notch1,implying that Prox1 could be a potential therapeutic target for RB.展开更多
Introduction: Actors of psychoactive drug initiation refer to those who introduce others to psychoactive drug use (initiators) and those who are introduced to psychoactive drugs (users). By identifying their features,...Introduction: Actors of psychoactive drug initiation refer to those who introduce others to psychoactive drug use (initiators) and those who are introduced to psychoactive drugs (users). By identifying their features, better prevention and intervention programs can be developed to reduce psychoactive drug use among adolescents. This article describes the role of actors of psychoactive drug initiation among teenagers in secondary schools in Yaoundé (Cameroon). Methodology: A cross sectional study was carried out in twelve secondary schools in Yaoundé from October 2022 to May 2023. Adolescents from Form four to upper sixth, who assented to participate in the study and received parental consent were included. Data were collected in a structured self-reported questionnaire and analyzed using SPSS 23. Quantitative variables were expressed using means, standard deviations, median and interquartile ranges depending on the distribution of data. Qualitative variables were expressed in the form of frequency and percentages. Results: Drug use was more prevalent among male adolescents (55.3%) from nuclear families (91.4%) who received relatively high pocket money. The main sources of drug exposure were non-family members (49.7%), especially friends outside school. The most frequent place of initiation was snack bars (33.1%). Conclusion: The study revealed the importance of the family, friends and leisure places in the initiation process of drug use in teenagers. Based on these results, parents and school authorities should work together to create a safe and supportive environment that fosters communication, education to prevent drug abuse among adolescents in Yaoundé.展开更多
Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack ...Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).展开更多
The spread of tuberculosis(TB),especially multidrug-resistant TB and extensively drug-resistant TB,has strongly motivated the research and development of new anti-TB drugs.New strategies to facilitate drug combination...The spread of tuberculosis(TB),especially multidrug-resistant TB and extensively drug-resistant TB,has strongly motivated the research and development of new anti-TB drugs.New strategies to facilitate drug combinations,including pharmacokinetics-guided dose optimization and toxicology studies of first-and second-line anti-TB drugs have also been introduced and recommended.Liquid chromatography-mass spectrometry(LC-MS)has arguably become the gold standard in the analysis of both endo-and exo-genous compounds.This technique has been applied successfully not only for therapeutic drug monitoring(TDM)but also for pharmacometabolomics analysis.TDM improves the effectiveness of treatment,reduces adverse drug reactions,and the likelihood of drug resistance development in TB patients by determining dosage regimens that produce concentrations within the therapeutic target window.Based on TDM,the dose would be optimized individually to achieve favorable outcomes.Pharmacometabolomics is essential in generating and validating hypotheses regarding the metabolism of anti-TB drugs,aiding in the discovery of potential biomarkers for TB diagnostics,treatment monitoring,and outcome evaluation.This article highlighted the current progresses in TDM of anti-TB drugs based on LC-MS bioassay in the last two decades.Besides,we discussed the advantages and disadvantages of this technique in practical use.The pressing need for non-invasive sampling approaches and stability studies of anti-TB drugs was highlighted.Lastly,we provided perspectives on the prospects of combining LC-MS-based TDM and pharmacometabolomics with other advanced strategies(pharmacometrics,drug and vaccine developments,machine learning/artificial intelligence,among others)to encapsulate in an all-inclusive approach to improve treatment outcomes of TB patients.展开更多
基金supported by the National Natural Science Foundation of China(No.71373089).
文摘Objective:Generic drugs provide an opportunity for savings in drug expenditure since they are available at a lower cost and do not affect patients’health.A better understanding of pharmacists’knowledge,attitudes,and perception can promote the quality use of generic drugs.The objective of this study was to investigate the knowledge,attitudes,and perception of pharmacists from tertiary hospitals in China regarding generic drugs.Methods:A cross-sectional survey using a postal questionnaire was conducted,which was sent to 200 hospital pharmacists randomly selected from tertiary hospitals in Hubei Province.A total of 125 questionnaires out of 200 were received.Of the respondents,80 were female and 45 were male.Results:The majority of respondents(87.2%)could clearly distinguish between original and generic drugs.Pharmacists agreed that generic drugs were less effective(52.8%)and produced more side effects(52%).Forty-nine respondents thought that generic drug products were not adequately tested.Approximately 78% and 60% of the pharmacists indicated that generic substitution was not feasible for drugs with narrow therapeutic windows and drugs for critical diseases,respectively.Most of them supported the recommendation of generic drugs based on professional judgment.Conclusion:Our study showed that a considerable portion of Chinese hospital pharmacists hold negative perceptions of generic drugs.Interventions to improve pharmacists'knowledge of generic drugs are needed.
文摘Development of generic drug product by pharmaceutical industry is a scientific and technical approach which is totally different from developing a reference or innovator product. Most of the developing countries focus on developing the generic drug products because huge amount of investment is required for innovation and to develop reference product. The generic medicine has to be bioequivalent to the innovator drug and ensure the same biological effect with proper safety and efficacy. Nowadays, the pharmaceutical industries focus on the development of generic product as this does not require that much time and cost compared to the innovator company. But development of generic product is also difficult as it contains the same therapeutic efficacy as innovator. The development approach is based on the target market, i.e. US market, EU market. If a manufacturer targets the US market, then all excipients should be USP grade, analysis should be conducted by USP method or in-house method and stability studies as well. Prior and during the development of generic drug product API selection, dosage form selection, reference product selection and characterization, formulation development, analytical method development, tech transfer or submission batch are prime concern. Then again, bioequivalence study, drug registration procedure and commercialization of the generic product considering regulatory guidance of respective regulatory agencies and the approaches taken by the regulatory agencies for the development of registration of generic medicines are also crucial as well for the development of generic drug product. The aim of this study was to review the entire stage of a generic drug development by a generic pharmaceutical company.
文摘Objective To study the significance of authorized generic drugs due to the successive relevant documents issued by China’s government in recent years,which clearly stipulated that China should establish a drug patent linkage system.Methods The authorized generic drugs play an important role in keeping the balance between brandname drugs and generic drugs in the US.Therefore,this system was investigated,focusing on its difference from independent generics,marketing procedures,application in patent litigation and legitimacy analysis through case evidence.This analogy analysis could provide a reference for the research of authorized generic drug systems in China.Results and Conclusion As an important factor affecting the balance between brand-name drugs and generic drugs,authorized generic drugs should be comprehensively analyzed and discussed,and a suitable system for China’s national conditions should be established by referring to the experiences of the US.
文摘Objective To study the impact of consistency evaluation policy on pharmaceutical enterprises from four aspects:reference preparations,evaluation methods,input costs,and market competitions,and government incentives for generic drug manufacturers,so as to put forward relevant suggestions.Methods Literature research method and statistical analysis method were used to provide data support for paper writing,making suggestions,and enhancing the predictability of policy.Results and Conclusion Some pharmaceutical enterprises faced difficulties in obtaining reference preparations,high input costs for exploring evaluation methods,and greater market competition.Consistency evaluation is a key measure to comprehensively improve the quality and efficacy of generic drugs.However,difficulties in obtaining reference preparations,high input costs and complex evaluation methods all affect the enthusiasm of companies.Therefore,national and local regulatory agencies have issued some supporting policies,which should be improved to assist enterprises in conducting consistency evaluations.
文摘Recently,generic drug products have played an increasingly important role in the health care system globally,especially in the developing world,as they provide for an effective and more affordable alternative for healthcare professionals.Generic drug products are proven therapeutically equivalent to the corresponding innovator’s product,and hence can be substituted in clinical practice.The objective of generic drug development is to develop a stable and bioequivalent generic drug product with desirable properties in a timely manner.This presentation is intended to summarize three important sequential stages essential for successful generic drug development based on a regulatory experience in reviewing and evaluating the Pharmaceutical Development Section(P2)of the ASEAN Common Technical Dossier(ACTD)of generic drug product applications submitted to the Food and Drug Administration,Thailand[1,2].
文摘The key events in the development of the US generic drug industry after the Hatch-Waxman Act of 1984 are systematically reviewed,including the process of approval for generic drugs,bioequivalence issues including“switchability”,bioequivalence for complicated dosage forms,patent extension,generic drug safety,generic substitution and low-cost generics.The backlog in generic review,generic drug user fees,and“quality by design”for generic drugs is also discussed.The evolution of the US generic drug industry after the Hatch-Waxman Act in 1984 has afforded several lessons of great benefit to other countries wishing to establish or re-establish a domestic generic drug industry.
文摘Veterinary drugs are substances(including pharmaceutical feed additives)used to prevent,treat,and diagnose diseases or regulate the physiological functions of animals.Veterinary drug poisoning in humans is relatively rare both in China and the rest of the world.Here,we report a case of death from veterinary drug poisoning from avermectin-closantel.Avermectin-closantel is a broad-spectrum antiparasitic drug,which has high efficacy against a variety of trematodes and nematodes.
基金supported by funding from the Bluesand Foundation,Alzheimer's Association(AARG-21-852072 and Bias Frangione Early Career Achievement Award)to EDan Australian Government Research Training Program scholarship and the University of Sydney's Brain and Mind Centre fellowship to AH。
文摘Tauopathies,diseases characterized by neuropathological aggregates of tau including Alzheimer's disease and subtypes of fro ntotemporal dementia,make up the vast majority of dementia cases.Although there have been recent developments in tauopathy biomarkers and disease-modifying treatments,ongoing progress is required to ensure these are effective,economical,and accessible for the globally ageing population.As such,continued identification of new potential drug targets and biomarkers is critical."Big data"studies,such as proteomics,can generate information on thousands of possible new targets for dementia diagnostics and therapeutics,but currently remain underutilized due to the lack of a clear process by which targets are selected for future drug development.In this review,we discuss current tauopathy biomarkers and therapeutics,and highlight areas in need of improvement,particularly when addressing the needs of frail,comorbid and cognitively impaired populations.We highlight biomarkers which have been developed from proteomic data,and outline possible future directions in this field.We propose new criteria by which potential targets in proteomics studies can be objectively ranked as favorable for drug development,and demonstrate its application to our group's recent tau interactome dataset as an example.
基金supported by the National Natural Science Foundation of China(Nos.51975400 and 62031022)Shanxi Provincial Key Medical Scientific Research Project(Nos.2020XM06 and 2021XM12)+3 种基金Fundamental Research Program of Shanxi Province(No.202103021224081)Shanxi Provincial Basic Research Project(Nos.202103021221006 and 202103021223040)Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(No.2021L044)Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering(No.2022SX-TD026).
文摘Traditional tumor models do not tend to accurately simulate tumor growth in vitro or enable personalized treatment and are particularly unable to discover more beneficial targeted drugs.To address this,this study describes the use of threedimensional(3D)bioprinting technology to construct a 3D model with human hepatocarcinoma SMMC-7721 cells(3DP-7721)by combining gelatin methacrylate(GelMA)and poly(ethylene oxide)(PEO)as two immiscible aqueous phases to form a bioink and innovatively applying fluorescent carbon quantum dots for long-term tracking of cells.The GelMA(10%,mass fraction)and PEO(1.6%,mass fraction)hydrogel with 3:1 volume ratio offered distinct pore-forming characteristics,satisfactorymechanical properties,and biocompatibility for the creation of the 3DP-7721 model.Immunofluorescence analysis and quantitative real-time fluorescence polymerase chain reaction(PCR)were used to evaluate the biological properties of the model.Compared with the two-dimensional culture cell model(2D-7721)and the 3D mixed culture cell model(3DM-7721),3DP-7721 significantly improved the proliferation of cells and expression of tumor-related proteins and genes.Moreover,we evaluated the differences between the three culture models and the effectiveness of antitumor drugs in the three models and discovered that the efficacy of antitumor drugs varied because of significant differences in resistance proteins and genes between the three models.In addition,the comparison of tumor formation in the three models found that the cells cultured by the 3DP-7721 model had strong tumorigenicity in nude mice.Immunohistochemical evaluation of the levels of biochemical indicators related to the formation of solid tumors showed that the 3DP-7721 model group exhibited pathological characteristics of malignant tumors,the generated solid tumors were similar to actual tumors,and the deterioration was higher.This research therefore acts as a foundation for the application of 3DP-7721 models in drug development research.
文摘Multiple sclerosis(MS)is an autoimmune disorder of the central nervous system(CNS)and is primarily characterized by immune cell infiltration leading to relapses followed by remission phases and a disease course turning progressive over time with neurodegenerative processes taking over(Amin and Hersh,2023).Of note,beyond relapse-associated worsening early in disease progression independent of relapse activity may arise independently of relapse activity and can occur in all phenotypes.Autoimmune-mediated damage of myelin sheaths and the subsequent loss of mature oligodendrocytes are resulting in impaired axonal integrity,neurodegeneration and accounts for irreversible neuronal damage(Kuhlmann et al.,2023).The current landscape of available disease-modifying therapies comprises mainly immunomodulatory drugs that effectively diminish relapses and slow down progression at the onset form of the disease,namely relapsing MS(RMS).In this regard,a number of drugs have been approved as disease-modifying therapies for MS by US Food and Drug Administration and European Medicines Agencies(Box 1).
基金supported by grants from the National Natural Science Foundation of China (Grant No. U20A20369)GuangDong Basic and Applied Basic Research Foundation (Grant No. 2022B1515120085)。
文摘Cancer immunotherapy has emerged as a promising approach in cancer treatment and is considered a major advancement after surgical interventions, radiotherapy, chemotherapy, and targeted therapy. The clinical use of immunotherapeutic drugs, particularly antibody-based drugs that target immune checkpoints, has notably increased~1.
文摘Percutaneous coronary interventions have progressed through the era of plain balloon dilation, bare-metal stent insertion to drug-eluting stent treatment, which has significantly reduced the acute occlusion and restenosis rates of target vessels and improved patient prognosis, making drug-eluting stents the mainstream interventional treatment for coronary artery disease. In recent years, drug-coated balloons(DCBs) have become a new treatment strategy for coronary artery disease, and the drugs used in the coating and the coating technology have progressed in the past years. Without permanent implant, a DCB delivers antiproliferative drugs rapidly and uniformly into the vessel wall via the excipient during a single balloon dilation. Many evidence suggests that DCB angioplasty is an effective measure for dealing with in-stent restenosis and de novo lesions in small coronary vessels.As more clinical studies are published, new evidence is emerging for the use of DCB angioplasty in a wide range of coronary diseases, and the indications are expanding internationally. Based on the latest research from China and elsewhere, the Expert Writing Committee of the Chinese Expert Consensus on Clinical Applications of Drug-Coated Balloon has updated the previous DCB consensus after evidence-based discussions and meetings in terms of adequate preparation of in-stent restenosis lesions, expansion of the indications for coronary de novo lesions, and precise guidance of DCB treatment by intravascular imaging and functional evaluation.
文摘The main aim of antineoplastic treatment is to maximize patient benefit by augmenting the drug accumulation within affected organs and tissues,thus incrementing drug effects and,at the same time,reducing the damage of non-involved tissues to cytotoxic agents.Mesenchymal stromal cells(MSC)represent a group of undifferentiated multipotent cells presenting wide self-renewal features and the capacity to differentiate into an assortment of mesenchymal family cells.During the last year,they have been proposed as natural carriers for the selective release of antitumor drugs to malignant cll,s thus optimizing cytotoxic action on cancer cll,while significantly reducing adverse side efect on healthy cells.MSC chemotherapeutic drug loading and delivery is an encouraging new area of cell therapy for several tumors,especially for those with unsatisfactory prognosis and limited treatment options available.Although some experim ental models have been sucesfuly developed,phase I dinical studies are needed to confirm this potential application of cell therapy,in particular in the case of primary and secondary lung cancers.
文摘Some bacteria have the ability to co-exist, proliferate and survive in a multicellular community, biofilm. Each participating bacteria can form its colonies and encases itself by a self-produced insoluble extracellular matrix substance (EPS). Microcolonies within biofilm are held together by interactions and bonding of the substances present in the EPS with their separation from the water channels. Similar to insoluble EPS, bacterial microcolonies release soluble exofactors that have direct impacts on the survivability, growth and antibacterial resistivity of other microcolonies made of single- or multi-species bacteria in the same biofilm. How the exofactors of microcolonies of one-type bacteria impact on microcolonies of other-type bacteria is still unclear. We studied about the role of exofactors released from Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa, which are common biofilm-forming pathogenic bacteria. Exofactors facilitate to transform the microenvironment where bacteria can acquire alternative lifestyle with a long survival period and resistivity to certain antimicrobial drugs.
基金Supported by Science and Technology Innovation Plan for Medical Workers in Shandong Province(SDYWZGKCJH2023095)Clinical Pharmacy Research Project of Shandong Provincial Medical Association(YXH2022ZX010)+1 种基金Traditional Chinese Medicine Science and Technology Development Project of Shandong Province(2019-0400&2021Q097)Traditional Chinese Medicine Research Program of Qingdao City(2020-zyy031)Medical Research Guidance Plan of Qingdao City(2020-WJZD087).
文摘[Objectives]To establish a new management model for rational use of perioperative antibacterial drugs in surgical departments.[Methods]Based on evidence-based medicine,the department s drug pathway was formulated,and the new mode of rational drug use control was established by using fine pharmaceutical technology intervention,and the intervention effect was evaluated by the intensity of antibacterial drug use,per capita drug costs and the proportion of drugs.[Results]After adopting drug pathway in departments,the intensity of antibacterial drug use,per capita drug costs and the proportion of drugs decreased significantly,and the effect of rational drug use control was remarkable.[Conclusions]The drug pathway provides a new management and control mode for the rational use of perioperative antibacterial drugs in surgical departments of hospitals.Thus,it is worthy of popularization and application.
文摘Introduction: The epidemiology of both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among drug users (DUs) is little known in West Africa. The study aimed to assess the prevalence of hepatitis B and C viruses among drug users in Burkina Faso. Methodology: This was a cross-sectional biological and behavioral survey conducted between June and August 2022, among drug users in Ouagadougou and Bobo Dioulasso, the two main cities of Burkina Faso. A respondent-driven sampling (RDS) was used to recruit drug users. Hepatitis B surface antigen was determined using lateral flow rapid test kits and antibodies to hepatitis C virus in serum determined using an Enzyme-Linked Immunosorbent Assay. Data were entered and analyzed using Stata 17 software. Weighted binary logistic regression was used to identify the associated factors of hepatitis B and C infections and a p-value Results: A total of 323 drug users were recruited with 97.5% males. The mean age was 32.7 years old. The inhaled or smoked mode was the most used by drug users. The adjusted hepatitis B and hepatitis C prevalence among study participants were 11.1% and 2.3% respectively. The marital status (p = 0.001), and the nationality (p = 0.011) were significantly associated with hepatitis B infection. The type of drug used was not significantly associated with hepatitis B infection or hepatitis C infection. Conclusion: The prevalence of HBsAg and anti-HCV antibodies among DUs are comparable to those reported in the general population in Burkina Faso. This result suggests that the main routes of contamination by HBV and HCV among DUs are similar to those in the population, and could be explained by the low use of the injectable route by DUs in Burkina Faso.
文摘Objective Retinoblastoma(RB)is a prevalent type of eye cancer in youngsters.Prospero homeobox 1(Prox1)is a homeobox transcriptional repressor and downstream target of the proneural gene that is relevant in lymphatic,hepatocyte,pancreatic,heart,lens,retinal,and cancer cells.The goal of this study was to investigate the role of Prox1 in RB cell proliferation and drug resistance,as well as to explore the underlying Notch1 mechanism.Methods Human RB cell lines(SO-RB50 and Y79)and a primary human retinal microvascular endothelial cell line(ACBRI-181)were used in this study.The expression of Prox1 and Notch1 mRNA and protein in RB cells was detected using quantitative real time-polymerase chain reaction(RT-qPCR)and Western blotting.Cell proliferation was assessed after Prox1 overexpression using the Cell Counting Kit-8 and the MTS assay.Drug-resistant cell lines(SO-RB50/vincristine)were generated and treated with Prox1 to investigate the role of Prox1 in drug resistance.We employed pcDNA-Notch1 to overexpress Notch1 to confirm the role of Notch1 in the protective function of Prox1.Finally,a xenograft model was constructed to assess the effect of Prox1 on RB in vivo.Results Prox1 was significantly downregulated in RB cells.Overexpression of Prox1 effectively decreased RB cell growth while increasing the sensitivity of drug-resistant cells to vincristine.Notch1 was involved in Prox1’s regulatory effects.Notch1 was identified as a target gene of Prox1,which was found to be upregulated in RB cells and repressed by increased Prox1 expression.When pcDNA-Notch1 was transfected,the effect of Prox1 overexpression on RB was removed.Furthermore,by downregulating Notch1,Prox1 overexpression slowed tumor development and increased vincristine sensitivity in vivo.Conclusion These data show that Prox1 decreased RB cell proliferation and drug resistance by targeting Notch1,implying that Prox1 could be a potential therapeutic target for RB.
文摘Introduction: Actors of psychoactive drug initiation refer to those who introduce others to psychoactive drug use (initiators) and those who are introduced to psychoactive drugs (users). By identifying their features, better prevention and intervention programs can be developed to reduce psychoactive drug use among adolescents. This article describes the role of actors of psychoactive drug initiation among teenagers in secondary schools in Yaoundé (Cameroon). Methodology: A cross sectional study was carried out in twelve secondary schools in Yaoundé from October 2022 to May 2023. Adolescents from Form four to upper sixth, who assented to participate in the study and received parental consent were included. Data were collected in a structured self-reported questionnaire and analyzed using SPSS 23. Quantitative variables were expressed using means, standard deviations, median and interquartile ranges depending on the distribution of data. Qualitative variables were expressed in the form of frequency and percentages. Results: Drug use was more prevalent among male adolescents (55.3%) from nuclear families (91.4%) who received relatively high pocket money. The main sources of drug exposure were non-family members (49.7%), especially friends outside school. The most frequent place of initiation was snack bars (33.1%). Conclusion: The study revealed the importance of the family, friends and leisure places in the initiation process of drug use in teenagers. Based on these results, parents and school authorities should work together to create a safe and supportive environment that fosters communication, education to prevent drug abuse among adolescents in Yaoundé.
基金supported by the National Natural Science Foundation of China(81825009,82071505,81901358)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2MC&T-B-099,2019-I2M-5–006)+2 种基金the Program of Chinese Institute for Brain Research Beijing(2020-NKX-XM-12)the King’s College London-Peking University Health Science Center Joint Institute for Medical Research(BMU2020KCL001,BMU2019LCKXJ012)the National Key R&D Program of China(2021YFF1201103,2016YFC1307000).
文摘Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).
基金sponsored by the National Research Foundation of Korea(NRF)Grant funded by the Korean government(MSIT)(Grant No.:2018R1A5A2021242).
文摘The spread of tuberculosis(TB),especially multidrug-resistant TB and extensively drug-resistant TB,has strongly motivated the research and development of new anti-TB drugs.New strategies to facilitate drug combinations,including pharmacokinetics-guided dose optimization and toxicology studies of first-and second-line anti-TB drugs have also been introduced and recommended.Liquid chromatography-mass spectrometry(LC-MS)has arguably become the gold standard in the analysis of both endo-and exo-genous compounds.This technique has been applied successfully not only for therapeutic drug monitoring(TDM)but also for pharmacometabolomics analysis.TDM improves the effectiveness of treatment,reduces adverse drug reactions,and the likelihood of drug resistance development in TB patients by determining dosage regimens that produce concentrations within the therapeutic target window.Based on TDM,the dose would be optimized individually to achieve favorable outcomes.Pharmacometabolomics is essential in generating and validating hypotheses regarding the metabolism of anti-TB drugs,aiding in the discovery of potential biomarkers for TB diagnostics,treatment monitoring,and outcome evaluation.This article highlighted the current progresses in TDM of anti-TB drugs based on LC-MS bioassay in the last two decades.Besides,we discussed the advantages and disadvantages of this technique in practical use.The pressing need for non-invasive sampling approaches and stability studies of anti-TB drugs was highlighted.Lastly,we provided perspectives on the prospects of combining LC-MS-based TDM and pharmacometabolomics with other advanced strategies(pharmacometrics,drug and vaccine developments,machine learning/artificial intelligence,among others)to encapsulate in an all-inclusive approach to improve treatment outcomes of TB patients.
