Inhibitory effect of diltiazem on diazepam metabolism in the mouse hepatic microsomes.
In order to elucidate the drug interaction between diltiazem and diazepam, the effect of diltiazem on the N-demethylation of diazepam in the mouse hepatic microsomes was investigated. Kinetic study showed that diltiazem noncompetitively inhibited the N-demethylation of diazepam with inhibition constant (Ki) value of 247.8 microM, indicating that diltiazem exhibits an inhibitory effect on the hepatic oxidative metabolism of diazepam. It was therefore suggested that diltiazem may impair the metabolism of diazepam in vivo.
Ihara
N
N
Department of Hospital Pharmacy, Kyoto Prefectural University of Medicine, Japan.
Kokufu
T
T
Sugioka
N
N
Ohta
T
T
Nosaka
K
K
D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D003975:Diazepam / Q000378:metabolism* / Q000493:pharmacokinetics; D004110:Diltiazem / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D003708:Nordazepam / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors
D065607:Cytochrome P-450 Enzyme Inhibitors; D003708:Nordazepam; D003577:Cytochrome P-450 Enzyme System; D010089:Oxidoreductases, N-Demethylating; C067539:diazepam N-demethylase; D004110:Diltiazem; D003975:Diazepam