Kinetics and inhibition by fluvoxamine of phenacetin O-deethylation in V79 cells expressing human CYP1A2.
The kinetics of phenacetin O-deethylation and its inhibition by fluvoxamine was investigated in a V79 cell line (V79MZh1A2) transfected with human CYP1A2. In four sets of experiments the apparent Km values for phenacetin O-deethylation ranged from 35 to 95 microM and the Ki for fluvoxamine-mediated inhibition of the reaction ranged from 2.7 to 14.5 nM, i.e. comparable to values obtained in human liver microsomes. The kinetic performance of the V79MZh1A2 cell line demonstrates its usefulness as an analytical tool in a variety of toxicological and drug metabolism studies involving CYP1A2.
Jensen
K G
KG
Department of Pharmacology, University of Copenhagen, Denmark.
Poulsen
H E
HE
Doehmer
J
J
Loft
S
S
D000082:Acetaminophen / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D019388:Cytochrome P-450 CYP1A2; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D016666:Fluvoxamine / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D010615:Phenacetin / Q000378:metabolism*; D014162:Transfection
D065607:Cytochrome P-450 Enzyme Inhibitors; D000082:Acetaminophen; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019388:Cytochrome P-450 CYP1A2; D010615:Phenacetin; D016666:Fluvoxamine