Yasui N
Department of Neuropsychiatry, Hirosaki University Hospital, Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 1996 Jun;16(3):109-12.
To clarify the involvement of cytochrome P4503A (CYP3A) and CYP2C19 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.
为阐明细胞色素P4503A（CYP3A）和CYP2C19在阿普唑仑代谢中的作用，在12名健康男性志愿者中研究了CYP3A抑制剂红霉素和S-美芬妥因4-羟化能力对阿普唑仑单次口服剂量动力学的影响。S-美芬妥因4-羟化的广泛代谢者（EMs）和慢代谢者（PMs）各6名。每位受试者以双盲、交叉方式接受10天的红霉素1200mg/天或安慰剂治疗。在第8天上午9点口服给予阿普唑仑0.8mg，并在给药后48小时内进行血样采集。与安慰剂治疗相比，红霉素治疗使给药后6至48小时的血浆阿普唑仑浓度显著升高。红霉素显著降低了阿普唑仑的表观口服清除率并延长了其消除半衰期。EM组和PM组之间阿普唑仑的血浆浓度和药代动力学参数未发现显著差异。因此，本研究表明CYP3A而非CYP2C19参与阿普唑仑的代谢。
