Planning and Evaluation of Bioequivalence Studiesof Enalapril Products

Ведомости Научного центра экспертизы средств медицинского применения

卷:8

D. P. Romodanovsk¹  A. E. Miroshnikov²  A. L. Khokhlov² 

[1] Scientific Centre for Expert Evaluation of Medicinal Products;

[2] Yaroslavl State Medical University;

关键词: bioequivalence study;    highly variable drugs;    inhibitors of angiotensin-converting enzyme;    enalapril;    enalaprilat;   

DOI  :  10.30895/1991-2919-2018-8-4-231-237

来源: DOAJ

【 摘 要 】

Nowadays retrospective analysis of bioequivalence studies of medicinal products that have the same International Nonproprietary Name is becoming particularly relevant. Over the past years we have accumulated a sufficient pool of data in the Russian Federation which make it possible to identify many differences, difficulties and errors associated with bioequivalence studies (especially those of highly variable drugs). Given that inhibitors of angiotensin-converting enzyme (ACE) can be highly variable, we conducted a retrospective analysis of bioequivalence studies of domestically-produced and foreign-made generic enalapril products. This article presents the results of the analysis whose aim was to determine intraindividual coefficients of variation and harmonise approaches to planning and evaluation of enalapril bioequivalence studies. It was demonstrated that enalapril products do not show high variability – both in terms of the original compound and the active metabolite. However, the analysis revealed many differences in the study designs: recruitment of a different number of healthy volunteers; determination of the concentration of either the original compound only, or in combination with the active metabolite; various analytical methods used for determination of analytes; different duration of blood sampling; and different sampling time points. The revealed differences made it possible to standardise the key research parameters, to harmonise them with the current requirements for conducting bioequivalence studies, and to formulate recommendations for planning and evaluation of enalapril studies. With respect to the study design, in addition to the standard conditions, the following can be recommended: at least 18 healthy volunteers should participate in enalapril bioequivalence studies; the pharmacokinetic parameters should be determined for both enalapril and its main active metabolite (enalaprilat); the duration of blood analyte determination should be at least 24 hours; the washout period should be 7 days; blood sampling for estimation of the maximum concentration should be more frequent around one hour after administration for enalapril and after three hours for enalaprilat.

【 授权许可】

Unknown