Weber F, Becquemont L
Laboratoire Parke Davis, département de pharmacovigilance, Courbevoie, France.
Therapie. 2000 Jul-Aug;55(4):569-75.
Liver drug metabolism is a major source of drug interactions. Three major human in vitro models are employed to detect drug interactions in the preclinical phases of drug development: recombinant enzymes, human liver microsomes and primary human hepatocyte cell cultures. Results obtained from these models may vary during the different phases of drug development. Identification of the metabolic pathways, enzymes involved in drug metabolism (mainly cytochrome P450s), enzyme induction or inhibition allow us to detect the major pharmacokinetic drug interactions which can occur in man and to identify specific populations at risk for such interactions. In vitro models are essential to decide if and which future drug interaction studies should be performed in man. However, the clinical relevance of the potential pharmacokinetic drug interactions detected by these in vitro models remains to be determined and confirmed by human studies.
肝脏药物代谢是药物相互作用的主要来源。在药物研发的临床前阶段，有三种主要的人体体外模型用于检测药物相互作用：重组酶、人肝微粒体和原代人肝细胞培养物。从这些模型获得的结果在药物研发的不同阶段可能会有所不同。确定代谢途径、参与药物代谢的酶（主要是细胞色素P450s）、酶诱导或抑制，有助于我们检测可能在人体中发生的主要药代动力学药物相互作用，并识别存在此类相互作用风险的特定人群。体外模型对于决定是否以及应该在人体中进行哪些未来的药物相互作用研究至关重要。然而，这些体外模型检测到的潜在药代动力学药物相互作用的临床相关性仍有待人体研究来确定和证实。
