Rendić S
Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb, P.O. Box 156, A. Kovacica 1, 10000 Zagreb, Croatia.
Croat Med J. 1999 Sep;40(3):357-67.
This paper reviews the main steps in the research of the interactions of H2-receptor antagonist drugs with cytochrome P450 (CYP) enzymes. Cimetidine, ranitidine, and related compounds are used as examples. The results from in vitro studies are related to the observed clinically significant in vivo drug-drug and drug-chemical interactions. Uses of the in vitro results are discussed for the interpretation and possible prediction of drug-drug interactions, which may be important in developing new drugs. Other approach in the use of the in vitro data is to prevent undesirable and toxic actions of drugs related to the catalytic activity of CYP enzymes. In the case of H2-receptor antagonists, the inhibition of the metabolic reactions due to the binding of the drugs with the enzymes was used to avoid side effects of co-administered drugs. The in vitro metabolic studies using recombinant human as well as animal CYP enzymes are now widely used as model syste ms for designing new drugs with improved therapeutic properties.
本文综述了H2受体拮抗剂药物与细胞色素P450（CYP）酶相互作用研究的主要步骤。以西咪替丁、雷尼替丁及相关化合物为例。体外研究结果与观察到的临床上显著的体内药物-药物和药物-化学相互作用相关。讨论了体外研究结果在药物-药物相互作用的解释和可能预测中的应用，这在新药开发中可能很重要。使用体外数据的另一种方法是预防与CYP酶催化活性相关的药物不良和毒性作用。就H2受体拮抗剂而言，利用药物与酶结合对代谢反应进行抑制以避免联用药物的副作用。目前，使用重组人及动物CYP酶进行的体外代谢研究被广泛用作设计具有改善治疗特性新药的模型系统。
