Therapeutic Drug Monitoring 2003-08-01

Effects of itraconazole on the plasma kinetics of quazepam and its two active metabolites after a single oral dose of the drug.

Kimiyasu Kato, Norio Yasui-Furukori, Takashi Fukasawa, Toshiaki Aoshima, Akihito Suzuki, Muneaki Kanno, Koichi Otani

Index: Ther. Drug Monit. 25(4) , 473-7, (2003)

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Abstract

The effects of itraconazole, a potent inhibitor of cytochrome P450 (CYP) 3A4, on the plasma kinetics of quazepam and its two active metabolites after a single oral dose of the drug were studied. Ten healthy male volunteers received itraconazole 100 mg/d or placebo for 14 days in a double-blind randomized crossover manner, and on the fourth day of the treatment they received a single oral 20-mg dose of quazepam. Blood samplings and evaluation of psychomotor function by the Digit Symbol Substitution Test and Stanford Sleepiness Scale were conducted up to 240 h after quazepam dosing. Itraconazole treatment did not change the plasma kinetics of quazepam but significantly decreased the peak plasma concentration and area under the plasma concentration-time curve of 2-oxoquazepam and N-desalkyl-2-oxoquazepam. Itraconazole treatment did not affect either of the psychomotor function parameters. The present study thus suggests that CYP 3A4 is partly involved in the metabolism of quazepam.