Pharmacogenetic perspectives in improving pharmacokinetic profiles for efficient bioequivalence trials with highly variable drugs: a review

摘要

Conducting bioequivalence trials under traditional crossover study designs without exposing a large number of healthy volunteers to demonstrate two highly variable (coefficient of variability greater than 30) test/reference (branded) drug products in different formulations to meet the standard 90 confidence interval criteria of relevant pharmacokinetic metrics between 0.80 and 1.25 and to maintain the consumer risk smaller than 5 has been a challenging task. Genetic polymorphisms encoding key drug-metabolizing enzymes can significantly influence absorption, distribution, metabolism and elimination of many highly variable generic drugs after administration. This article briefly reviews the case studies and examples of utilizing pharmacogenetic screening approaches in the recent literature to alleviate the resources and ethical burden of recruiting larger numbers of subjects in bioequivalence trials needed to perform pharmacokinetic studies for formulations of highly variable drug products without widening the bioequivalence acceptance limits.