Sartori E, Delaforge M
Université René Descartes, UA 400 CNRS, Laboratoire de Chimie et Biochimie, Paris, France.
Chem Biol Interact. 1990;73(2-3):297-307. doi: 10.1016/0009-2797(90)90010-k.
Clinical interactions of macrolides with various drugs lead to elimination impairment, increase of plasma concentration and overdose-like effects, resulting from modifications of their metabolism. Previous studies have shown that treatment of rats by the macrolide antibiotics of the oleandomycin and erythromycin series lead to the induction of an hepatic cytochrome P-450 which is implicated into their own metabolism. We have characterized PCN or macrolides induced cytochromes P-450 by their specific ability to interact with macrolide derivatives and, using the cytochrome P-450 spectral binding assays, we have shown that some compounds, implicated in drug interaction with macrolides, interact preferentially with the same cytochromes. This strongly suggests that specific blockage of cytochrome P-450 IIIA1 family by macrolides, is responsible for these drug interactions and that these interactions can be predicted easily by simple in vitro tests such as those described herein.
大环内酯类药物与各种药物的临床相互作用会导致代谢改变，进而引起消除障碍、血药浓度升高及类似过量用药的效应。先前的研究表明，用竹桃霉素和红霉素系列的大环内酯类抗生素治疗大鼠会诱导一种参与自身代谢的肝细胞色素P - 450。我们通过与大环内酯衍生物相互作用的特定能力对青霉素或大环内酯类诱导的细胞色素P - 450进行了表征，并且利用细胞色素P - 450光谱结合试验表明，一些与大环内酯类存在药物相互作用的化合物优先与相同的细胞色素相互作用。这有力地表明，大环内酯类对细胞色素P - 450 IIIA1家族的特异性阻断是这些药物相互作用的原因，并且这些相互作用可以通过本文所述的简单体外试验轻松预测。
