Role of CYP1A2 in caffeine pharmacokinetics and metabolism: studies using mice deficient in CYP1A2
作者:
Jeroen Buters,
Bing-Kou Tang,
Thierry Pineau,
Harry Gelboin,
Shioko Kimura,
Frank Gonzalez,
期刊:
Pharmacogenetics
(OVID Available online 1996)
卷期:
Volume 6,
issue 4
页码: 291-296
ISSN:0960-314X
年代: 1996
出版商: OVID
关键词: CYP1A2;caffeine;pharmacokinetics;metabolism;urine;knockout mice
数据来源: OVID
摘要:
We investigated the involvement of CYP1A2 in the pharmacokinetics and metabolism of caffeine using mice lacking its expression (CYP1A2-/-). The half-life of caffeine elimination from blood was seven times longer in the CYP1A2 -/- than wild-type mice. The clearance was concomitantly eight times slower. No parameter that could affect the pharmacokinetics differed between CYP1A2 -/- and wild-type mice such as creatinine for kidney function; alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and bilirubin for liver function; or albumin for protein binding. Other P450s CYP2A, 2B, 2C, 2E1, and 3A were also unchanged in the knockout animals. Caffeine 3-demethylated metabolites thought previously to be characteristic of CYP1A2 (especially 1 -methylxanthine and 1-methylurate) were also found in the urines of the CYP1A2 -/- animals, although at 40% of the level found in wild-type mice. These data indicate that the clearance of caffeine in wild-type mice is primarily determined by CYP1A2.
点击下载:
PDF
(469KB)
返 回