Le Dinh T, Christoforov B
Laboratories Roussel Uclaf, Romainville.
Therapie. 1994 Mar-Apr;49(2):133-40.
Interindividual variability of hepatic metabolism of drugs may be responsible for decrease in efficacy, increase in the incidence and severity of adverse effects or drug-interactions. This variability may be due to hepatic drug interaction, specific physio-pathologic condition or genetic polymorphism. Search for variability of hepatic metabolism and the factors determining this variability during the pre-clinical and clinical development of new drug contributes to an individual optimization of treatment during clinical research and after introduction into the market. This strategy results in an improvement of the benefit-risk ratio. The various methodological approaches to the study of hepatic metabolism during the successive phases of drug development and the integration of these studies in the clinical development plan of a new drug are discussed in this paper.
药物肝脏代谢的个体间差异可能导致疗效降低、不良反应发生率及严重程度增加或药物相互作用。这种差异可能归因于肝脏药物相互作用、特定的生理病理状况或基因多态性。在新药临床前和临床开发过程中寻找肝脏代谢的差异以及决定这种差异的因素，有助于在临床研究期间及上市后实现个体化治疗优化。这一策略可改善效益风险比。本文讨论了在药物开发的连续阶段研究肝脏代谢的各种方法学途径，以及将这些研究纳入新药临床开发计划的情况。
