INVIVO EFFECTS OF ERYTHROMYCIN, OLEANDOMYCIN AND ERYTHRALOSAMINE DERIVATIVES ON HEPATIC CYTOCHROME-P-450

被引:18
作者
DELAFORGE, M
SARTORI, E
机构
[1] Université René Descartes, UA 400 CNRS, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, 75270 Paris Cedex 06
关键词
D O I
10.1016/0006-2952(90)90682-B
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Rats have been treated with several derivatives of the erythromycin, erythralosamine or oleandomycin series, in order to compare their ability to induce cytochrome P-450 and to form stable 456 nm-absorbing cytochrome P-450 metabolite complexes. The data obtained that the cytochromes P-450 induced in rats by various macrolides are similar to that induced by pregnenolone 16α-carbonitrile: the cytochrome P-450 IIIA1 isozyme. It showed that: (i) formation of a stable inhibitory 456 nm-absorbing cytochrome P-450 complex is not a prerequisite for cytochrome P-450 induction but enhances induction by stabilization of the IIIA isozyme. Therefore, the best inducers lead also to the maximal in vivo amounts of cytochrome P-450 metabolite complex (except for 2′MBEM); (ii) affinity for cytochrome P-450 IIIA1 is not directly involved for induction; and (iii) hydrophobicity favors induction and formation of complexes. Structural factors are also involved. © 1990.
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页码:223 / 228
页数:6
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