AIMS:The aim of this study was to investigate the effects of roflumilast, an investigational PDE4 inhibitor for the treatment of COPD and asthma, on the pharmacokinetics of the CYP3A probe drug midazolam and its major metabolites. METHODS:In an open, randomized (for midazolam treatment sequence) study, 18 healthy male subjects received single doses of midazolam (2 mg oral and 1 mg i.v., 1 day apart) alone, repeated doses of roflumilast (500 microg once daily for 14 days) alone, and repeated doses of roflumilast together with single doses of midazolam (2 mg oral and 1 mg i.v., 1 day apart). RESULTS:A comparison of clearance and peak and systemic exposure to midazolam following administration of roflumilast indicated no effect of roflumilast dosed to steady state on the pharmacokinetics of midazolam. Point estimates (90% CI) were 0.97 (0.84, 1.13) for the AUC of i.v. midazolam and 0.98 (0.82, 1.17) for that of oral midazolam with and without roflumilast. CONCLUSIONS:Therapeutic steady state concentrations of roflumilast and its N-oxide do not alter the disposition of the CYP3A substrate midazolam in healthy subjects. This finding suggests that roflumilast is unlikely to alter the clearance of drugs that are metabolized by CYP3A4.

译文

目的:本研究的目的是研究用于研究COPD和哮喘的PDE4抑制剂罗氟司特对CYP3A探针药物咪达唑仑及其主要代谢物的药代动力学。
方法:在一项开放,随机(针对咪达唑仑治疗序列)的研究中,18名健康男性受试者单独接受单剂量的咪达唑仑(2 mg口服和1 mg iv,相隔1天),重复剂量的鲁氟司特(500 microg,每天一次,共14剂)天),重复剂量的罗氟司特和单剂量的咪达唑仑(2 mg口服和1 mg iv,间隔1天)。
结果:比较使用氟氟司特后咪达唑仑的清除率,峰和全身暴露的清除率,表明洛氟司特剂量稳定后对咪达唑仑的药代动力学没有影响。 i.v. AUC的点估计值(90%CI)为0.97(0.84,1.13)。咪达唑仑和口服咪达唑仑含或不含roflumilast的口服咪达唑仑均为0.98(0.82,1.17)。
结论:罗氟司特及其氮氧化物的治疗稳态浓度不会改变CYP3A底物咪达唑仑在健康受试者中的分布。该发现表明罗氟司特不太可能改变被CYP3A4代谢的药物的清除率。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录