Role of CYP1A2 in caffeine pharmacokinetics and metabolism: Studies using mice deficient in CYP1A2

Jeroen T.M. Buters, Bing Kou Tang, Thierry Pineau, Harry V. Gelboin, Shioko Kimura, Frank J. Gonzalez

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

68 Zitate (Scopus)

Abstract

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; alkaline 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-demethyIated 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.

OriginalspracheEnglisch
Seiten (von - bis)291-296
Seitenumfang6
FachzeitschriftPharmacogenetics
Jahrgang6
Ausgabenummer4
DOIs
PublikationsstatusVeröffentlicht - 1996
Extern publiziertJa

Fingerprint

Untersuchen Sie die Forschungsthemen von „Role of CYP1A2 in caffeine pharmacokinetics and metabolism: Studies using mice deficient in CYP1A2“. Zusammen bilden sie einen einzigartigen Fingerprint.

Dieses zitieren