Induction of the metabolism of etizolam by carbamazepine in humans.
OBJECTIVE
To examine the effect of carbamazepine on the single oral dose pharmacokinetics of etizolam.


METHODS
Eleven healthy male volunteers received carbamazepine 200 mg/day or placebo for 6 days in a double-blind, randomized, crossover manner, and on the sixth day they received a single oral 1-mg dose of etizolam. Blood samplings and evaluation of psychomotor function by the Digit Symbol Substitution Test and Stanford Sleepiness Scale were conducted up to 24 h after etizolam dosing. Plasma concentration of etizolam was measured using high-performance liquid chromatography.


RESULTS
Carbamazepine treatment significantly decreased the peak plasma concentration (17.5+/-4.1 ng/ml versus 13.9+/-4.1 ng/ml; P<0.05), total area under the plasma concentration-time curve (194.8+/-88.9 ng h/ml versus 105.9+/-33.0 ng h/ml; P<0.001), and elimination half-life (11.1+/-4.6 h versus 6.8+/-2.8 h; P<0.01) of etizolam. No significant change was induced by carbamazepine in the two pharmacodynamic parameters.


CONCLUSIONS
The present study suggests that carbamazepine induces the metabolism of etizolam.
Kondo
S
S
Department of Psychiatry, Yamagata University School of Medicine, Yamagata, 990-9585, Japan.
Fukasawa
T
T
Yasui-Furukori
N
N
Aoshima
T
T
Suzuki
A
A
Inoue
Y
Y
Tateishi
T
T
Otani
K
K
D000284:Administration, Oral; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D019540:Area Under Curve; D002220:Carbamazepine / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D003975:Diazepam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D014149:Tranquilizing Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics
D018712:Analgesics, Non-Narcotic; D014149:Tranquilizing Agents; D002220:Carbamazepine; C044610:etizolam; D003975:Diazepam