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Original Article |
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Neuropsychopharmacology (1998) 18 364-369.10.1038/sj.npp.1395147
Effect of Carbamazepine on the Single Oral Dose Pharmacokinetics of Alprazolam
Hanako Furukori1 MD, Koichi Otani3 MD, Ph.D, Norio Yasui1 MD, Ph.D, Tsuyoshi Kondo1 MD, Ph.D, Sunao Kaneko1 MD, Ph.D, Ritsuko Shimoyama2 BS, Tadashi Ohkubo2 Ph.D, Takako Nagasaki2 BS and Kazunobu Sugawara2 Ph.D |
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1Department of Neuropsychiatry, Hirosaki University Hospital, Hirosaki, Japan
2Pharmacy, Hirosaki University Hospital, Hirosaki, Japan
3Department of Neuropsychiatry, Yamagata University School of Medicine, Yamagata, Japan
Correspondence: Dr Tsuyoshi Kondo, Department of Neuropsychiatry, Hirosaki University Hospital, Hon-cho 53, Hirosaki 036, Japan
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ABSTRACT
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The effect of carbamazepine, an inducer of cytochrome P450 (CYP) 3A4, on the single oral dose pharmacokinetics of alprazolam was examined in a double-blind, randomized crossover study with two phases. Seven healthy male subjects took carbamazepine 300 mg/day or matched placebo orally for 10 days, and on the 8th day they took a single oral 0.8 mg dose of alprazolam. Blood samples were taken and psychomotor function was assessed by the Digit Symbol Substitution Test, Visual Analog Scale, and UKU Side Effect Rating Scale up to 48 h after alprazolam dosing. Carbamazepine significantly (p < .01 to .001) decreased the plasma alprazolam concentrations during the elimination phase. Carbamazepine significantly (p < .001) increased the apparent oral clearance (0.90 ± 0.21 vs. 2.13 ± 0.54 ml/min/kg) and shortened the elimination half-life (17.1 ± 4.9 vs. 7.7 ± 1.7 h), with no significant effect on the peak plasma concentration (11.7 ± 1.5 vs. 13.0 ± 3.5 ng/ml). The majority of psychomotor function parameters during the carbamazepine treatment were not significantly different from those during the placebo treatment, probably because of the sedative effect of carbamazepine itself. The present study suggests that carbamazepine decreases plasma concentration of alprazolam by inducing its metabolism. It also supports the previous studies, suggesting that alprazolam is metabolized predominantly by CYP3A4.
Keywords: Alprazolam; Carbamazepine; Single oral dose; Pharmacokinetics; Metabolism; CYP3A4 |
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