Clinical efficacy and modeling evaluation of He-wei-zhi-xie capsules in treating diarrhea patients / 中国临床药理学与治疗学

AIM: To evaluate the clinical efficacy and safety of He-wei-zhi-xie (HWZX) capsules in diarrhea patients. METHODS: The clinical study was conducted in 35 clinical trials centers from October 2015 to December 2017 by multicenter, prospective, open and uncontrolled design methods. The primary efficacy endpoint is the effective rate of diarrhea, the secondary endpoints include recovery rate of diarrhea, recovery time of diarrhea, number of irregular stools and Leeds dyspepsia questionnaire. The pharmacodynamics model of time course was established by nonlinear mixed effect model, and the effect of covariates on pharmacodynamic parameters was investigated. The safety measures were the incidence of adverse events, adverse reactions and the laboratory test indicators. RESULTS: A total of 2 285 cases were included in full analysis set. The effective rate of diarrhea was 90.8%, and the diarrhea recovery rate was 77.3%. The median time of recovery was 3 days, and the Leeds score was reduced by 3.6 points. It is found that baseline has a significant effect on model parameter E

Study on the Implementation of American Post-marketing Re-evaluation of Drugs Legal System and Its Enlightenment to China / 中国药房

OBJECTIVE： To provide reference for the establishment and improvement of the post-marketing re-evaluation of drugs （shorted for re-evaluation） legal system in China. METHODS： Through sorting out American re-evaluation system， this paper focused on the current situation and procedures of the implementation of American re-evaluation system and put forward the suggestions for improving drug re-evaluation system in China. RESULTS & CONCLUSIONS： American re-evaluation system takes enterprises as the main body of execution and the government as the main body of supervision. It has the characteristics of highly informatized and transparent process. The work includes the report of ADR implementation of monitoring systems， the periodic reporting system and the post-listing clinical trials and research systems. The implementation process is to find clues， FDA preliminary review and notification， enterprise further self-examination and review， corporate actions and accept FDA supervision. It is suggested that when establishing the legal system of re-evaluation system in China， the main role of patients should be highlighted， and risk communication should be guided by the public. For example， the Medwatch voluntary reporting system of FDA can be imitated. The unified data collection， storage system and scientific data processing methods can be established. Continuously strengthen the main responsibility consciousness of pharmaceutical enterprises in testing and reporting， and constantly reduce the risk of drug use of patients.

Post-marketing study on clinical safety of ginkgo diterpene lactone meglumine injection in 6 300 patients with ischemic stroke / 中国中药杂志

To further evaluate the safety of ginkgo diterpene lactone meglumine injection in the clinical use in ischemic stroke patients. Clinical safety study was conducted in 82 clinical units and 6 300 cases were completed and included from June 2013 to December 2014 by using multicenter, prospective, open and uncontrolled design methods for clinical research. A total of 29 cases of adverse reactions were observed in the experiment. Adverse reaction ratio (ADR) was 0.46%, and about 86.21% (25 cases) of them was mild with transient response which could be alleviated or disappeared without intervention; about 13.79% (4 cases) was moderate, including 2 cases of headache, 1 case of dizziness and 1 case of rash; no serious adverse reactions were found. The adverse reactions occurred in this study were pre-known adverse reactions or common adverse reactions of Chinese medicine injection. The overall incidence of adverse reactions was low, and the risk was controllable.

Post-marketing reevaluation on bioequivalence of metformin hydrochloride tablets / 中国药学杂志

OBJECTIVE: To reevaluate the bioequivalence of post-marketing metformin hydrochloride tablets. METHODS: With the original metformin hydrochloride tablets (Glucophage) as the reference preparation, the in vitro dissolution of Glucophage and generic metformin hydrochloride tablets from eight pharmaceutical factories (A-H) was investigated using method 1 described in the appendix X C in Chinese Pharmacopoeia (edition 2010), among which two generic products were chosen for the bioequivalence study as test 1 and test 2 preparations. In a randomized, three-way crossover study, 24 healthy male volunteers were given a single oral dose of test 1, test 2 and reference preparations containing 500 mg of metformin hydrochloride. Plasma concentrations of metformin were determined by LC-MS/MS. The pharmacokinetic parameters and relative bioavailability were calculated. The bioequivalence between test 1 and reference preparation, test 2 and reference preparation, and the bioequivalence between the two test preparations were evaluated. RESULTS: The in vitro dissolution of the metformin hydrochloride tablets from all the nine factories met the standard of Chinese Pharmacopoeia (edition 2010). Metformin hydrochloride tablets from factory B and H, of which the cumulative dissolution rate-time profiles were significantly different from that of Glucophage, were chosen to be test 1 and test 2 preparations, respectively. The F0-t and F0-∞ were (102.0±13.3)% and (101.9±13.3)% for test 1 preparation, and (94.6±14.7)% and (94.4±14.5)% for test 2 preparation to Glucophage. Both test 1 and test 2 preparations were bioequivalent with reference preparation, and the two test preparations were also bioequivalent. CONCLUSION: The bioinequivalence risk of metformin hydrochloride tablets is low. Biowaivers can be granted for generic metformin hydrochloride tablets on the basis of in vitro dissolution evaluation, to save cost, improve efficiency in drug development and supervision, and reduce unnecessary drug exposure in human body.

Post-marketing reevaluation of bioequivalence of metformin hydrochloride enteric-coated tablets / 中国药学杂志

OBJECTIVE: To reevaluate the bioequivalence of marked metformin hydrochloride enteric-coated tablets. METHODS: Using method 2 described in the appendix X D and apparatus 1 described in the appendix X C in Chinese Pharmacopoeia(edition 2010), the in vitro release of metformin hydrochloride enteric-coated tablets from different pharmaceutical factories (A, B, C, and D) was investigated. The contents were measured by utlraviolet (UV) spectroscopy. Generic tablets from factory A and D were chosen to be test 1 and test 2 preparations, with the innovative metformin hydrochloride tablets (Glucophage) as the reference preparation. In a randomized, three-way crossover study, 21 healthy male volunteers were given a single oral dose of test 1, test 2 and reference preparations containing 500 mg of metformin hydrochloride. Plasma concentrations of metformin were determined by LC-MS/MS. The pharmacokinetic parameters and relative bioavailability were calculated. The bioequivalence between test 1 and reference preparation, test 2 and reference preparation, and the bioequivalence between the two test preparations were evaluated. RESULTS: The in vitro release of metformin hydrochloride enteric-coated tablets from factory B, C and D met the standard of Chinese Pharmacopoeia(the supplement edition of 2010) while that of the tablets from factory A did not. Metformin hydrochloride enteric-coated tablets from factory A and D were chosen to be test 1 and test 2 preparations, respectively. The F0-t and F0-∞ were (72.8 ± 9.7)% and (73.2 ± 10.0)% for test 1 preparation, and (45.5 ± 16.2)% and (46.2 ± 16.0)% for test 2 preparation, respectively. It was failed to conclude that test 1 and reference preparation were bioinequivalent. Test 2 and reference preparation were bioinequivalent, and the two test preparations were also bioinequivalent. CONCLUSION: The bioinequivalence risk of metformin hydrochloride enteric-coated tablets is high. For metformin hydrochloride enteric-coated tablets, not only conducting pre-marketing bioequivalence study with proper reference preparation, but also enhancing post-marketing surveillance and reevaluation of bioequivalence are very important for maintaining the consistency of drugs quality. Copyright 2012 by the Chinese Pharmaceutical Association.