Effects of itraconazole on the plasma kinetics of quazepam and its two active metabolites after a single oral dose of the drug.
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.
Kato
Kimiyasu
K
Department of Neuropsychiatry, Yamagata University School of Medicine, Yamagata, Japan.
Yasui-Furukori
Norio
N
Fukasawa
Takashi
T
Aoshima
Toshiaki
T
Suzuki
Akihito
A
Kanno
Muneaki
M
Otani
Koichi
K
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001569:Benzodiazepines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004311:Double-Blind Method; D004347:Drug Interactions; D005479:Flurazepam / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D017964:Itraconazole / Q000008:administration & dosage*; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects; D012890:Sleep / Q000187:drug effects
D065607:Cytochrome P-450 Enzyme Inhibitors; D006993:Hypnotics and Sedatives; D001569:Benzodiazepines; D017964:Itraconazole; C039103:2-oxoquazepam; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D005479:Flurazepam; C025130:quazepam; C020965:norflutoprazepam