DRUGDEX DRUG EVALUATIONS数据库介绍

DRUGDEX DRUG EVALUATIONS数据库主要收录基于实时证据,针对药品临床使用信息编撰而成的独立专论。本文简要介绍DRUGDEX数据库的数据开发流程、专论内容及组织结构、检索方法和获取途径等,目的是为医药专业人员提供一个药品评价信息的参考资源。

A Few Specialized Issues That Should Be Focused on Anti-HIV Drug Evaluation In Vitro

Since the introduction of antiretroviral therapy (ART), the lifespan and quality of life of patients infected with HIV have been significantly improved. But treatment efficacy was compromised eventually by the development of resistance to antiretroviral drugs, and more new anti-HIV drugs with lower toxicity and higher activity were needed. Based on the experience and lessons learned from the treatment in the developed countries, US FDA suggested that more pharmacodynamical researches should be considered ahead of the clinical trials. To facilitate the anti-HIV drug research and development, we reviewed a few specialized issues that should be focused on drug evaluations in vitro, including: 1) Mechanism of action studies, demonstrating the candidate drug's efficacy to specifically inhibit viral replication or a virus-specific function and confirm the drug target. 2) Drug resistance studies, selecting the drug-resistant variants in vitro and determining the activities inhibiting HIV isolates resistant to approved antiretroviral drugs of the same class. 3) Antiviral activity in vitro in the presence of serum proteins, ascertaining whether an investigational product is significantly bound by serum proteins. 4) Combination activity analysis, evaluating in vitro antiviral activity of an investigational product in two-drug combinations with other drugs approved.

Construction of Non-infectious SARS-CoV-2 Replicons and Their Application in Drug Evaluation

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a devastating pandemic worldwide.Vaccines and antiviral drugs are the most promising candidates for combating this global epidemic,and scientists all over the world have made great efforts to this end.However,manipulation of the SARS-CoV-2 should be performed in the biosafety level3 laboratory.This makes experiments complicated and time-consuming.Therefore,a safer system for working with this virus is urgently needed.Here,we report the construction of plasmid-based,non-infectious SARS-CoV-2 replicons with turbo-green fluorescent protein and/or firefly luciferase reporters by reverse genetics using transformation-associated recombination cloning in Saccharomyces cerevisiae.Replication of these replicons was achieved simply by direct transfection of cells with the replicon plasmids as evident by the expression of reporter genes.Using SARS-CoV-2 replicons,the inhibitory effects of E64-D and remdesivir on SARS-CoV-2 replication were confirmed,and the halfmaximal effective concentration(EC50)value of remdesivir and E64-D was estimated by different quantification methods respectively,indicating that these SARS-CoV-2 replicons are useful tools for antiviral drug evaluation.

Facile fabrication of drug-loaded PEGDA microcapsules for drug evaluation using droplet-based microchip

Droplet-based microfluidic technology can be utilized as a microreactor to prepare novel functional monodisperse microcapsules.In this study,a droplet-based microfluidic chip with surface modification,which allowed the one-step preparation of double emulsion microcapsules.An O/W/O double emulsion using polyethylene(glycol)diacrylate(PEGDA)solution as the intermediate water phase was prepared by regulating the hydrophilicity and hydrophobicity of the chip surface,with PEGDA microcapsules prepared using UV polymerization.And then anti-tumor drug paclitaxel and neurotoxin 6-OHDA were encapsulated in microcapsules for drug and toxicology evaluation,respectively.Compared to controls,drug-loaded mi-crocapsules caused a significant increase in the death rate of PC12 cells.This indicates that the obtained drug-loaded microcapsules could be used in drug evaluation and potentially in drug screening and deliv-ery.

Drug utilization evaluation of medications used in the management of neurological disorders

Background and object:The burden of neurological disorders in India is expected to increase due to the rapid demographic and epidemiological transition,with irrational drug use,which is also a global concern.Thus,drug utilization evaluation is designed to ensure appropriate medicine use within the healthcare settings.The aim of the study was to assess the rate and pattern of drug utilization in the management of neurological disorders.Materials and methods:A hospital-based cross-sectional drug utilization evaluation study on neurological drugs was carried out at the Department of Neurology over a span of six months.All legible prescriptions consisting neurological medications irrespective of patient's gender,aged≥18 years were included for the study.The World Health Organization(WHO)core drug use indicators were used to assess the drug prescribing and utilization patterns.Results:A total of 310 prescriptions were reviewed,where male predominance was found to be 56.45%.Out of 310 prescriptions,drugs belonging to 26 neurological classes were prescribed for the management of various neurological disorders.The majority of patients were diagnosed with epilepsy and the most prescribed drugs per patient were phenytoin(14.8%)and valproic acid(6.45%).By following the WHO core drug prescribing indicators,65.47%of drugs prescribed from the India National List of Essential Medicines,2022,followed by 29.83%of drugs prescribed in generic name and 10.86%of prescriptions including injections.Conclusion:The study findings showed that the prescribing pattern in the Department of Neurology was in accordance with the WHO core prescribing indicators.But,the extent of polypharmacy prescriptions was very high.Therefore,interventions are very necessary to promote rational drug prescribing patterns and thus clinical pharmacists can contribute to assess and review the drug utilization pattern to optimize the drug therapy and improvement in patient safety.

<i>In Vitro</i>Evaluation of Anticancer Drugs with Kinetic and Static Alternating Cell Culture System

Variable bioreactors have been developed for the evaluation of anti-cancer drug efficacy. The Kinetic and Static Alternating Cell Culture System (KSACCS) combines the advantages of kinetic bioreactors and static cultures to improve cell growth by providing adequate metabolic support while minimizing shear-stress. In the current studies, the KSACCS in the ZYX Bioreactor could significantly increase the sensitivity of lung cancer cells (PLS008) and leukemia cells (HL60) to anticancer drugs Cisplatin and 5-FU by accelerating the apoptosis of cancer cells. It was also shown that excessive agitation of the cells could lead to severe cell damage, which resulted in a diminished sensitivity of anticancer drug evaluation, and co-culture systems tend to reduce the sensitivity of anticancer drug evaluation although it might better mimic in vivo conditions.

An Evaluation Synthesis of US AIDS Drug Assistance Program Policy

US Congress passed the CARE Act in 1990 in response to a dramatically growing need for resources to combat the AIDS epidemic. One of the programs contained in the Act was the AIDS Drug Assistance Program (ADAP), a federally-funded but state-maintained and managed program primarily concerned with providing medication for low-income HIV/AIDS patients. While ADAP programs across the country reached one-third of all patients in 2007, these programs are now in budgetary danger due to the economic recession, state budgetary constraints, the rising cost of healthcare generally, and longer life expectancies associated with current highly active antiretroviral therapy (HAART). This paper first evaluates the current state of ADAP, its strengths and weaknesses, and examines its sustainability in the short term if short-term measures are taken. Concluding that such measures would not lead to long-term sustainability, this paper then argues for a long-term solution to ADAP’s current problems, namely a national, centralized ADAP standard for budgetary and administrative matters. Such a program would increase the long-term sustainability and effectiveness of current ADAP programs by employing more efficient, standard policies and allowing larger, wholesale purchases of costly HAART medications. Moreover, a national policy would address the disparity that currently exists in ADAP programs today with regard to both minorities and those on the waiting lists for treatment. The institution of a national ADAP program would certainly face many political hurdles. Consequently, this paper also looks to a recent political dispute, the enactment of the Affordable Care Act (ACA), for guidance. Using the passage of the ACA as an example could light the path for passage of a national ADAP standard. Ultimately, this would lead to a more effective and sustainable program for HIV/AIDS patients in the United States.

The role of drug utilization evaluation in medical sciences

Background:Drug utilization evaluation(DUE)is defined by the World Health Organization(WHO)and focuses on the medical,social,and economic consequences of pharmaceutical marketing,distribution,prescribing,and usage in society.The WHO recommends a physician to every 1000 people.According to the recent data from the Health Ministry in 2019,in which 1.16 million doctors are of active population with just 80%,or 0.9 million,practicing.As a result,a ratio of 0.68 doctors for every 1000 people,which is much below as per the WHO reports.This article describes history,types,WHO guidelines,need and purpose of DUE.Objective:The main aim of this paper is to provide information about the rational use of medication in outpa­tient and inpatient department with special emphasis of DUEs.It also provides awareness directly to healthcare professionals,researchers,academicians,pharmacist and nurses to reduce the irrationality of medicines.Methods:The method used to compile this review information gathered from websites,Google scholar,PubMed,Research gate,and studies published on DUE from July 20 to Oct 22 were included as source of information.Results:We studied more than 35 published study on DUE,that reveals most of the physicians prescribed branded drugs not generic drugs,but WHO prescribing indicator allows to prescribe generic drugs in the hospital pharmacy to maintain better inventory control.It may also help to prevent pharmacist misunderstanding during dispensing.Conclusion:The use of generic prescription names avoids the possibility of medication product duplication and lowers patient costs.It is important to remember that incorrect medication prescriptions have impact on both patients and their family members.WHO indicators identify irrational prescribing behaviours to make therapy more rational and cost-effective.

The Problems of the Safety Evaluation of Biotechnology Derived Drugs

Recent years have witnessed rapid advances in the toxicologic assessment of biotechproducts.Safety assessment of a biotech product is a complex and multiple process.This includes a knowledge of its pharmaco-biological characteristics,and identifyingthe target patient population and the proposed clinical application. To make a decision on the safe human application(the products are administering tohumans for therapeutic purposes),besides the identity and purity of the final product,

Evaluation and Risk Prevention and Control of Hepatic Injury by Traditional Drugs

My topic is the risk assessment of safety of Chinese materia medica.Next I will take drug-induced hepatic injury as an example.First of all,let us look back at what Chinese materia medica is.What are the real meanings of these 3 words? These 3 words Zi Hua Zi have been said more than BC 500."TCM practitioners are for treatment and medicines," what do you mean? Treatment means to find the cause of the disease and to find the law,while medicine is to find ways and means to cure diseases.

The Impact of Generic Drug Consistency Evaluation Policy on Pharmaceutical Enterprises

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.

EVALUATION OF EFFICACY AND SAFETY OF DIACEREIN IN KNEE OSTEOARTHRITIS IN CHINESE PATIENTS

Objective To evaluate the efficacy and safety of diacerein in patients with knee osteoarthritis (OA). Methods A total of 223 patients satisfying the American College of Rheumatology criteria for knee OA were chosen for this 17-week, randomized, double-dummy, diclofenac sodium-controlled trial, with diacerein dosage of 100 mg/d and diclofenac sodium of 75mg/d. Efficacy and safety of both drugs were evaluated. Results Totally 106 patients in the diacerein group and 107 patients in the diclofenac group were considered qualified for the evaluation. After 12 weeks of treatment, the total effective rates of patients/physicians’ overall assessment in diacerein and diclofenac groups were 65.4%/61.6% and 61.2%/61.2%, respectively (P>0.05). The primary efficacy parameter [visual analog scale (VAS) assessment of pain on 20 metres walking] and the secondary efficacy parameters [tenderness on palpation, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and 36-item Short-Form (SF-36) Health Survey] significantly improved compared with baseline in both groups (P<0.05). In the follow-up period, there were no obvious changes in above parameters in diacerein group. However, in diclofenac group, pain on 20 metres walking, tenderness on palpation, and WOMAC became aggravated after withdrawing the drug for 4 weeks (P<0.05). Moreover, the consumption of paracetamol was significantly lower in diacerein group than in diclofenac group during follow-up (P<0.001). The incidences of related adverse events were 35.7% in diacerein and 45.1% in diclofenac group, respectively. Mild-to-moderate gastrointestinal disorders were the most frequent adverse events. Conclusions Diacerein is as effective as diclofenac sodium in treating patients with knee OA. Furthermore, it has better extended effect and a good safety profile. It is generally well tolerated and has no severe adverse effect.

Multi-factor combined biomarker screening strategy to rapidly diagnose Alzheimer's disease and evaluate drug effect based on a rat model

Alzheimer's disease(AD)represents the main form of dementia;however,valid diagnosis and treatment measures are lacking.The discovery of valuable biomarkers through omics technologies can help solve this problem.For this reason,metabolomic analysis using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS)was carried out on plasma,hippocampus,and cortex samples of an AD rat model.Based on the metabolomic data,we report a multi-factor combined biomarker screening strategy to rapidly and accurately identify potential biomarkers.Compared with the usual procedure,our strategy can identify fewer biomarkers with higher diagnostic specificity and sensitivity.In addition to diagnosis,the potential biomarkers identified using our strategy were also beneficial for drug evaluation.Multi-factor combined biomarker screening strategy was used to identify differential metabolites from a rat model of amyloid beta peptide 1e40(Aβ_(1-40))plus ibotenic acid-induced AD(compared with the controls)for the first time;lysophosphatidylcholine(LysoPC)and intermediates of sphingolipid metabolism were screened as potential biomarkers.Subsequently,the effects of donepezil and pine nut were successfully reflected by regulating the levels of the abovementioned biomarkers and metabolic profile distribution in partial least squaresdiscriminant analysis(PLS-DA).This novel biomarker screening strategy can be used to analyze other metabolomic data to simultaneously enable disease diagnosis and drug evaluation.

Identification and antibiotic susceptibility evaluation of Mycoplasma synoviae isolated from chickens in central China

Mycoplasma synoviae(M.synoviae)infections have become an increasingly serious concern in China because they cause huge economic losses to the poultry industry.Antibiotic treatment is one of control strategies that can be used to contain clinical outbreaks in M.synoviae-free flocks,especially because the bacteria can be transmitted through eggs.To understand M.synoviae infection status in farms of central China and the antibiotic susceptibility of the circulating strains in vivo and in vitro,485 samples were collected from five provinces from 2019 to 2021.Fifty-two strains were isolated and identified.Determination of the minimum inhibitory concentration(MIC)of eight antibiotics(tylvalosin,tiamulin,tilmicosin,lincomycin,enrofloxacin,chlortetracycline,doxycycline and tylosin)for isolates showed that tylvalosin,doxycycline and tiamulin were effective against 52 clinical isolates(MIC values≤0.0625-0.25μg/mL,≤0.0625-1μg/mL,and 0.25-2μg/mL,respectively).Tilmicosin,enrofloxacin and lincomycin had high MICo values(>32μg/mL).An artificial M.synoviae infection model was established in chickens for evaluation of the short-term therapeutic effect of these antibiotics.After 5 days of medication,doxycycline(200 mg/L)showed a superior ability to inhibit M.synoviae compared with other groups,as did tylvalosin(200 mg/L).Furthermore,the therapeutic efficacy of tylvalosin(0.4μg/mL)on intra-embryo-injected M.synoviae was higher than that of tiamulin at the same dose.A combination of MiC values determined in vitro and therapeutic effects observed in vivo revealed that tylvalosin and doxycycline had the best therapeutic effects.Tylvalosin also showed better inhibitory effects on the vertical transmis-sion of M.synoviae than tiamulin.

Efficacy of Jian’ganle(健肝乐) versus Hugan Pian(护肝片),Glucuronolactone and Reduced Glutathione in Prevention of Antituberculosis Drug-induced Liver Injury

Summary： Evidence-based medicine is advocated by WHO and adopted by developed countries for many years. In China, however, the selection of essential medicine and various medical insurance reimbursement schemes medicine is usually based on experts＇ experience of prescription practice which is under heavy critics resulting from the lack of related comparative efficacy and evidence-based research. The efficacy of Jian＇ganle in prevention of drug-induced liver injury （DILI） caused by antituberculotics was evaluated in this study by comparison with Hugan Pian, glucuronolactone and reduced glutathione. Evidence was provided for relevant sectors such as Ministry for Human Resources and Social Security of the People＇s Republic of China and National Health and Family Planning Commission of the Peo- ple＇s Republic of China to select and renew the Essential Medicine List （EML）, the new rural cooperative medical scheme in China （NRCMS） list or the reimbursement list of industrial injury insurance. A total of 189 patients with initial pulmonary tuberculosis were divided into four groups who took antituberculotics combined with Jian＇ganle, Hugan Pian, glucuronolactone and reduced glutathione respectively. Their liver function profile including alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, total bilirubin （TBIL）, direct bilirubin （DBIL）, total protein （TP）, albumin （A） and globulin （G） were detected at admission as baseline and after treatment. The Jian＇ganle group was compared with the three others by chi-square tests. In an aspect of maintaining bilirubin indexes normal, Jian＇ganle was more efficacious than glucuronolactone. And Jian＇ganle had a little more efficacy than reduced glutathione to maintain protein indexes normal as well. And the therapeutic regimen of antituberculotics combined with Jian＇ganle was the best in treating tuberculosis and preventing DILI at the same time. The study showed that among the four hepatinicas which demonstrated similar prevention of DILI caused by antituberculotics, Jian＇ganle has more advantages over the three others to some extent, which provides a reliable basis for health sectors to select and renew the EML, NRCMS List or the reimbursement list of industrial injury insurance.

Evaluation of directly observed treatment short courses at a secondary health institution in Ibadan,Oyo State,Southwestern Nigeria

Objective:To evaluate the success rate of tuberculosis intervention programme at a specialist hospital in(?)badan,Nigeria through a retrospective study as well as carry out physicochemical evaluation of anti-tuberculous agents as a way of eliminating drug-related failure.Methods:The retrospective study involved the use of quarterly tuberculosis central register at the Government Chest Hospital,(?)badan between 1st quarter(2003)to 4th quarter(2009).Relevant data were extracted from these register with the aid of data collection forms.The basic physicochemical analyses of the drugs given to the patients were also carried out using the International Pharmacopoeia methods.Results:All the drugs examined for their physicochemical properties passed the International Pharmacopeia recommended tests.A total number of 1 260 patients enrolled at the hospital were assessed through case notes.This comprises of 59.4%males of which69.23%new cases were also males.There was a significant(P<0.05)patient enrollment across the quarters for the seven years.An overall 80.24%cure rate over the 7-period was obtained which is less than the WHO target of 85%.Cure rates were better in females than males.Failure treatment outcomes such as positive(1.51%),deaths(8.73%),defaulted(3.33%)and transferred out(5.95%)were recorded though not statistically significant(P>0.05).Failure rates in all categories were higher in males than females(P>0.05).Conclusions:More enlightenment and counseling is still required to meet up with the target for TB control.

Preparation and evaluation of tamsulosin hydrochloride sustained-release pellets modified by two-layered membrane techniques

The aim of the present study was to develop tamsulosin hydrochloride sustained-release pellets using two-layered membrane techniques.Centrifugal granulator and fluidizedbed coater were employed to prepare drug-loaded pellets and to employ two-layered membrane coating respectively.The prepared pellets were evaluated for physicochemical characterization,subjected to differential scanning calorimetry(DSC)and in vitro release of different pH.Different release models and scanning electron microscopy(SEM)were utilized to analyze the release mechanism of Harnual■ and home-made pellets.By comparing the dissolution profiles,the ratio and coating weight gain of Eudragit■ NE30D and Eudragit■ L30D55 which constitute the inside membrane were identified as 18:1 and 10%-11%.The coating amount of outside membrane containing Eudragit■ L30D55 was determined to be 0.8%.The similarity factors(f_(2))of home-made capsule and commercially available product(Harnual■)were above 50 in different dissolution media.DSC studies confirmed that drug and excipients had good compatibility and SEM photographs showed the similarities and differences of coating surface between Harnual■ and self-made pellets before and after dissolution.According to Ritger-Peppas model,the two dosage form had different release mechanism.

A Protocol for Developing a Clinical Practice Guideline for Therapeutic Drug Monitoring of Vancomycin

This study aimed to develop a guideline for therapeutic drug monitoring（TDM） of vancomycin. We adopted the new guideline definition from the Institute of Medicine（IOM）, adhered closely to the six domains of the Appraisal of Guidelines for Research ＆ Evaluation Ⅱ（AGREE Ⅱ）, and made recommendations based on systematic reviews. We established a Guideline Steering Group and a Guideline Development Group, formulated 12 questions in the form of Population, Intervention, Comparison, Outcome（PICO） and completed a literature search. As far as we know, we will develop the first evidenced-based guideline for vancomycin TDM under the framework of the Grade of Recommendations Assessment, Development and Evaluation（GRADE）.

Quantitative characterization of cell physiological state based on dynamical cell mechanics for drug efficacy indication

Cell mechanics is essential to cell development and function,and its dynamics evolution reflects the physiological state of cells.Here,we investigate the dynamical mechanical properties of single cells under various drug conditions,and present two mathematical approaches to quantitatively characterizing the cell physiological state.It is demonstrated that the cellular mechanical properties upon the drug action increase over time and tend to saturate,and can be mathematically characterized by a linear timeinvariant dynamical model.It is shown that the transition matrices of dynamical cell systems significantly improve the classification accuracies of the cells under different drug actions.Furthermore,it is revealed that there exists a positive linear correlation between the cytoskeleton density and the cellular mechanical properties,and the physiological state of a cell in terms of its cytoskeleton density can be predicted from its mechanical properties by a linear regression model.This study builds a relationship between the cellular mechanical properties and the cellular physiological state,adding information for evaluating drug efficacy.

Effects of two novel sugar drug candidates on CYP450 isoforms in different sexed Chinese human liver microsome in vitro

The sex-based differences between the effects of two novel sugar-based drug candidates,a sulfated polymannuroguluronate(SPMG-911)and an acidic oligosaccharide sugar chain compound(AOSC-971),on the enzymes CYP 1A2,CYP2E1 and CYP3A4 of Chinese human liver microsome were investigated.The results showed that neither SPMG-911 nor AOSC-971 have any effect on CYP3A4,AOSC-971 induced the CYP 2E1 in men but have no effect on CYP1A2,SPMG-911 inhibit the CYP1A2 also in men but have no effect on CYP2E1.The results are useful for their safety evaluation,as well as for the prediction of inter-drug interactions associated with the two drugs.