Role of CYP1A2 in caffeine pharmacokinetics and metabolism: studies using mice deficient in CYP1A2.
Article Details
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Buters JT, Tang BK, Pineau T, Gelboin HV, Kimura S, Gonzalez FJ
Role of CYP1A2 in caffeine pharmacokinetics and metabolism: studies using mice deficient in CYP1A2.
Pharmacogenetics. 1996 Aug;6(4):291-6.
- PubMed ID
- 8873215 [ View in PubMed]
- 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; alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and bilirubin for liver function; or albumin for protein binding. Other P450s CYP2A, 2B, 2C, 2EI, and 3A were also unchanged in the knockout animals. Caffeine 3-demethylated metabolites thought previously to be characteristic of CYP1A2 (especially 1-methylxanthine and I-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.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Acefylline Cytochrome P450 1A2 Protein Humans NoSubstrateDetails Bamifylline Cytochrome P450 1A2 Protein Humans NoSubstrateDetails Bromotheophylline Cytochrome P450 1A2 Protein Humans NoSubstrateDetails Doxofylline Cytochrome P450 1A2 Protein Humans NoSubstrateDetails Etamiphylline Cytochrome P450 1A2 Protein Humans NoSubstrateDetails Fenethylline Cytochrome P450 1A2 Protein Humans NoSubstrateDetails Pentifylline Cytochrome P450 1A2 Protein Humans NoSubstrateDetails Propentofylline Cytochrome P450 1A2 Protein Humans UnknownSubstrateDetails Proxyphylline Cytochrome P450 1A2 Protein Humans NoSubstrateDetails