Meyer U A, Amrein R, Balant L P, Bertilsson L, Eichelbaum M, Guentert T W, Henauer S, Jackson P, Laux G, Mikkelsen H, Peck C, Pollock B G, Priest R, Sjöqvist F, Delini-Stula A
University of Basel, Department of Pharmacology, Switzerland.
Acta Psychiatr Scand. 1996 Feb;93(2):71-9. doi: 10.1111/j.1600-0447.1996.tb09805.x.
Antidepressant drugs are extensively metabolized. Consequently, the biotransformation pattern of antidepressants has an important influence on their clinical properties, i.e., pharmacokinetics, toxicity, drug-drug interactions, side-effect profile and last but not least therapeutic efficacy. It was against this background that a multidisciplinary group of experts discussed the clinical relevance of the rapidly increasing body of knowledge of antidepressant-metabolizing enzymes. The variability of the response of a given individual to an antidepressant is determined genetically and by the environment. Genetic polymorphism of drug-metabolizing enzymes and inhibition by other substrates may affect the enzymatic biotransformation of antidepressants. In vitro assay techniques allow an estimation of the potential variability in clinical response to antidepressants and a reasonable prediction of the drug-drug interaction patterns. The results of in vitro tests should therefore be considered early in the development of an antidepressant as a background for designing clinical studies (treatment schedules and dosing). Physicians should have an understanding of the relevance of genetic polymorphism for clinical practice. Education is needed in order to fill the existing gaps in knowledge about antidepressant-enzyme interactions and their application in daily treatment practice. The information on potential drug interactions determined by genetic polymorphism and based on studies with enzymes should be increasingly contained in drug compendia.
抗抑郁药物会被广泛代谢。因此，抗抑郁药物的生物转化模式对其临床特性具有重要影响，即药代动力学、毒性、药物相互作用、副作用概况，以及同样重要的治疗效果。正是在这一背景下，一个多学科专家小组讨论了抗抑郁药物代谢酶知识快速增长所具有的临床相关性。个体对某种抗抑郁药物反应的变异性由遗传因素和环境因素决定。药物代谢酶的基因多态性以及其他底物的抑制作用可能会影响抗抑郁药物的酶促生物转化。体外测定技术能够估计临床对抗抑郁药物反应的潜在变异性，并合理预测药物相互作用模式。因此，在抗抑郁药物研发早期，应将体外试验结果作为设计临床研究（治疗方案和给药剂量）的背景加以考虑。医生应该了解基因多态性在临床实践中的相关性。需要开展教育，以填补关于抗抑郁药物与酶相互作用及其在日常治疗实践中应用的现有知识空白。由基因多态性决定并基于酶的研究得出的潜在药物相互作用信息，应越来越多地纳入药物手册中。
