Rost K L, Mansmann U, Roots I
Institute of Clinical Pharmacology, Universitätsklinikum Benjamin Franklin, Free University of Berlin, Germany.
Int J Clin Pharmacol Ther. 1997 Jan;35(1):14-8.
Lansoprazole has been shown to induce cytochrome P450 1A (CYP1A) and CYP3A enzymes in human hepatocytes in vitro. In this study, urinary excretion of 6 beta-hydroxycortisol (6 beta-OHF) and D-glucaric acid (D-GA) were used to investigate the potential enzyme-inducing property of lansoprazole in vivo. Twenty-four healthy female volunteers (aged 19-35 years), who were taking oral contraceptives containing 0.03 mg ethinylestradiol and 0.15 mg levonorgestrel, were randomized in a cross-over design for the treatment with either 60 mg lansoprazole or placebo once daily during 2 subsequent menstrual cycles. Urinary excretion rates of 6 beta-OHF and D-GA were measured at days 14 and 21 of the menstrual cycles. Median pretreatment urinary excretion of 6 beta-OHF (212 and 218 micrograms/d, n = 24) and D-GA (20.1 and 32.7 mumol/d) did not significantly differ. Upon treatment median excretion of 6 beta-OHF was 255 and 241 micrograms/d (n = 23), and that of D-GA was 25.5 and 33.8 mumol/d, respectively. Thus, the relatively high dose of 60 mg/d lansoprazole failed to statistically significantly alter urinary excretion of 6 beta-OHF and D-GA, indicating that therapeutic doses of lansoprazole might not exhibit a phenobarbital-like induction in vivo.
体外研究表明,兰索拉唑可诱导人肝细胞中的细胞色素P450 1A(CYP1A)和CYP3A酶。在本研究中,通过检测6β-羟基皮质醇(6β-OHF)和D-葡萄糖醛酸(D-GA)的尿排泄量,来研究兰索拉唑在体内的潜在酶诱导特性。24名健康女性志愿者(年龄19 - 35岁),正在服用含0.03 mg炔雌醇和0.15 mg左炔诺孕酮的口服避孕药,采用交叉设计随机分组,在随后的两个月经周期中,每天一次分别服用60 mg兰索拉唑或安慰剂。在月经周期的第14天和第21天测量6β-OHF和D-GA的尿排泄率。6β-OHF(212和218微克/天,n = 24)和D-GA(20.1和32.7微摩尔/天)的治疗前尿排泄中位数无显著差异。治疗后,6β-OHF的排泄中位数分别为255和241微克/天(n = 23),D-GA的排泄中位数分别为25.5和33.8微摩尔/天。因此,60 mg/d的相对高剂量兰索拉唑未能在统计学上显著改变6β-OHF和D-GA的尿排泄,表明治疗剂量的兰索拉唑在体内可能不会表现出类似苯巴比妥的诱导作用。