The relationship between single-oral dose kinetics of alprazolam and cytochrome P4503A and cytochrome P4502C19
Yasui, N.
Nihon Shinkei Seishin Yakurigaku Zasshi 16(3): 109-112
1996
ISSN/ISBN: 1340-2544 PMID: 8905799 Document Number: 457673
To clarify the involvement of cytochrome P4503A (CYP3A) and CYP2Cl9 in the metabolism of alprazolam, the effects of pretreatment with erythromycin, which is an inhibitor of CYP3A and S-mephenytoin 4-hydroxylation capacity on the single-oral dose kinetics of alprazolam were studied in 12 healthy male volunteers. Six each were extensive metabolizers (EMs) and poor metabolizers (PMs) of S-mephenytoin 4-hydroxylation. Each subject received erythromycin 1,200 mg/day or placebo for 10 days in a double-blind, crossover manner. At 9 AM of day 8 alprazolam 0.8 mg was given orally, and blood samplings were performed up to 48 hours postdosing. Erythromycin treatment compared with placebo treatment increased significantly plasma alprazolam concentrations from 6 to 48 hours postdosing. Erythromycin significantly decreased the apparent oral clearance and prolonged the elimination half-life of alprazolam. No significant difference was found in plasma concentrations and pharmacokinetic parameters of alprazolam between the EM and PM groups. The present study thus suggests that CYP3A, but not CYP2C19, is involved in the metabolism of alprazolam.