Effects of Itraconazole on the Plasma Kinetics of Quazepam and Its Two Active Metabolites after a Single Oral Dose of the Drug
Effects of Itraconazole on the Plasma Kinetics of Quazepam and Its Two Active Metabolites after a Single Oral Dose of the Drug
复制标题
单次口服药物后伊曲康唑对夸西泮及其两种活性代谢物血浆动力学的影响
DOI：
10.1097/00007691-200308000-00010
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发表时间：
2003
影响因子：
2.5
通讯作者：
K. Otani
中科院分区：
文献类型：
--
作者：
Kimiyasu Kato;N. Yasui‐Furukori;T. Fukasawa;T. Aoshima;A. Suzuki;Muneaki Kanno;K. Otani
&NA;本文研究了细胞色素P450（CYP）3A 4的有效抑制剂伊曲康唑单次口服后对夸西泮及其两种活性代谢物的血浆动力学的影响。10名健康男性志愿者以双盲随机交叉方式接受伊曲康唑100 mg/d或安慰剂治疗14天，并在治疗第4天接受单次口服20 mg夸西泮。在quazepam给药后240 h进行血液采样和通过数字符号替代试验和斯坦福大学嗜睡量表进行精神功能评价。伊曲康唑治疗未改变夸西泮的血浆动力学，但显著降低了2-氧代夸西泮和N-去烷基-2-氧代夸西泮的血浆峰浓度和血药浓度-时间曲线下面积。伊曲康唑治疗不影响任何精神功能参数。因此，本研究表明，α 3A 4部分参与了夸西泮的代谢。
&NA; 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.