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单次给予6-氨基烟酰胺对大鼠肝脏微粒体药物代谢的影响。

Effects of a single administration of 6-aminonicotinamide on hepatic microsomal drug metabolism in rats.

作者信息

Sugiyama S, Satoh T, Uzalp B, Ueno K, Igarashi T, Kitagawa H

出版信息

Arch Int Pharmacodyn Ther. 1984 May;269(1):20-33.

PMID:6235789
Abstract

Pretreatment of rats with 6-aminonicotinamide (6-AN) induced a significant increase in aminopyrine (AM) N-demethylation and hexobarbital (HX) hydroxylation in rats. In this study, the concentrations of AM, 4-monomethylaminoantipyrine (MAA), aminoantipyrine (AA) and further metabolites were measured by using the GC/MS method. The increase in AM N-demethylation induced by 6-AN treatment was confirmed by measuring the area under the plasma concentration-time curve (AUC) for AM, MAA and AA in rats after AM administration. Of the first two steps of AM metabolism mediated by cytochrome P-450-coupled monooxygenase, the second step (from MAA to MA) was found to be more affected by 6-AN than the first one (from AM to MAA).

摘要

用6-氨基烟酰胺(6-AN)对大鼠进行预处理可导致大鼠氨基比林(AM)N-去甲基化和己巴比妥(HX)羟基化显著增加。在本研究中,采用气相色谱/质谱法测定了AM、4-单甲基氨基安替比林(MAA)、氨基安替比林(AA)及其进一步代谢产物的浓度。通过测量AM给药后大鼠血浆中AM、MAA和AA的浓度-时间曲线下面积(AUC),证实了6-AN处理诱导的AM N-去甲基化增加。在细胞色素P-450偶联单加氧酶介导的AM代谢的前两个步骤中,发现第二步(从MAA到MA)比第一步(从AM到MAA)受6-AN的影响更大。

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