Open questions on bioequivalence: some problems and some solutions.

摘要: This paper focuses on some specific situations where bioequivalence requires careful attention and tailored protocols in order to overcome intrinsic difficulties either marginally covered or fully neglected by operating guidelines. Some problems congregate with serious difficulties, namely high variability, very poorly absorbed drugs endogenous substances their own baseline. With substances, the dilemma faced is whether subtract baseline from post-dose values assessing bioequivalence. Either approach has somewhat puzzling. In an attempt resolve other existing problems, most appropriate should be selected a case-by-case basis, ensuring that adopted procedure does not conflict guidelines scientific literature matter. Problematic cases include management of trials predominant active metabolite, absence reliable analytical bioassay, availability various strengths same drug market, wide acceptability titre range, studies topical are devoid systemic activity, cannot given for ethical reasons healthy subjects may cause adverse events, especially when steady state design required. The parallel group study appears more than cross-over individual long half-life. pharmacokinetic statistical analysis-related issues also discussed such as sequence/period interaction sometimes encountered these trials, which, carry-over effect, bias results need process data non-compartmental analysis.