Effect of chlormethiazole on hepatic monooxygenases activity in vivo.
Chlormethiazole is a strong inhibitor of cytochrome P-450-dependent monooxygenases in isolated human liver microsomes. To assess its effect in vivo, we measured the pharmacokinetic parameters of antipyrine (1.2 g orally) and tolbutamide (0.5 g i.v.) before and after administration of chlormethiazole 314 mg b.d. for 2 days to 8 healthy volunteers. The elimination of neither substance was affected, indicating that chlormethiazole did not inhibit in vivo the cytochrome P-450 isozymes responsible for the elimination of antipyrine and tolbutamide.
Mönig
H
H
Medizinische Klinik, Christian-Albrechts-Universität, Kiel, Germany.
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D J
DJ
Heidemann
H T
HT
Ohnhaus
E E
EE
Brockmann
B
B
Schulte
H M
HM
D000983:Antipyrine / Q000493:pharmacokinetics; D002719:Chlormethiazole / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D014044:Tolbutamide / Q000493:pharmacokinetics
D002719:Chlormethiazole; D014044:Tolbutamide; D006899:Mixed Function Oxygenases; D000983:Antipyrine