Delaforge M, Sartori E
Université René Descartes, UA 400 CNRS, Paris, France.
Biochem Pharmacol. 1990 Jul 15;40(2):223-8. doi: 10.1016/0006-2952(90)90682-b.
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 confirm that the cytochromes P-450 induced in rats by various macrolides are similar to that induced by pregnenolone 16 alpha-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.
为了比较几种红霉素、红霉胺或竹桃霉素系列衍生物诱导细胞色素P - 450以及形成稳定的456nm吸收细胞色素P - 450代谢物复合物的能力，对大鼠进行了处理。获得的数据证实，各种大环内酯类药物在大鼠体内诱导产生的细胞色素P - 450与孕烯醇酮16α - 腈诱导产生的相似：细胞色素P - 450 IIIA1同工酶。结果表明：(i)形成稳定的456nm吸收的抑制性细胞色素P - 450复合物不是细胞色素P - 450诱导的先决条件，但通过稳定IIIA同工酶增强诱导作用。因此，最好的诱导剂也会导致体内细胞色素P - 450代谢物复合物的量达到最大（2'MBEM除外）；(ii)对细胞色素P - 450 IIIA1的亲和力与诱导作用没有直接关系；(iii)疏水性有利于诱导和复合物的形成。结构因素也起作用。
