In vitro metabolism of GV150013X by using liver microsomes and liver tissue slices from different species

被引：2

作者：

Kajbaf, M ^{[1
]}

Rossato, P ^{[1
]}

Ferrari, L ^{[1
]}

Grossi, P ^{[1
]}

Pellegatti, M ^{[1
]}

机构：

[1] Glaxo SpA, Med Res Ctr, Dept Drug Metab, I-37135 Verona, Italy

来源：

EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS | 1997年 / 22卷 / 04期

关键词：

thermospray mass spectrometry; GV150013X; metabolism; liver tissue slices; microsomes;

D O I：

10.1007/BF03190971

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The metabolism of GV150013X was studied in vitro using washed liver microsomes and liver tissue slices from different species. This work was carried out in order to compare the metabolite profiles resulting from incubation of GV150013X with human, rat, dog and rabbit liver microsomes and those from rat, rabbit and human liver tissue slices. This compound was found to be converted to at least 8 metabolites by rat and human liver microsomes. In rabbit liver microsomes, the three metabolites M4, M7 and M8, and in dog liver microsomes metabolite M1, were not detected. The main metabolites, M2, M5 and M6, were present in human, rat and rabbit liver tissue slices, while the three metabolites M3, M4 and M8 and metabolite Mi were not detected in rabbit and rat liver tissue slices, respectively. In rat liver tissue slices, the major metabolites plus five minor metabolites, one sulphate conjugate of a monohydroxylated, three trihydroxylated and one dihydroxylated were identified based on HPLC retention time and thermospray-mass spectrometry data. Quantitative species differences among rat, dog, rabbit and human were observed, while qualitative differences only between rabbit and other species were detected.

引用

页码：359 / 366

页数：8

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