阿扎那韦/利托那韦对健康女性中含有炔雌醇和诺孕酯的口服避孕药药代动力学的影响。

The effect of atazanavir/ritonavir on the pharmacokinetics of an oral contraceptive containing ethinyl estradiol and norgestimate in healthy women.

作者信息

Zhang Jenny, Chung Ellen, Yones Cynthia, Persson Anna, Mahnke Lisa, Eley Timothy, Xu Xiaohui, Bertz Richard

机构信息

Research and Development, Bristol-Myers Squibb, Princeton, NJ, USA.

出版信息

Antivir Ther. 2011;16(2):157-64. doi: 10.3851/IMP1724.

DOI:10.3851/IMP1724

PMID:21447864

Abstract

BACKGROUND

Coadministration of oral contraceptives with protease inhibitors is complicated by drug interactions. An open-label three-period single-sequence study assessed the effect of coadministration of atazanavir (ATV)/ritonavir (RTV) with Ortho Tri-Cyclen(®) and with Ortho Tri-Cyclen(®) LO (Ortho-McNeil-Janssen Pharmaceuticals, Inc., Raritan, NJ, USA) on the pharmacokinetics (PK) of ethinyl estradiol (EE), norgestimate (NGM), ATV and RTV.

METHODS

A total of 20 healthy women aged 18-45 years received study treatments. In the lead-in period and in period 1, participants received a full cycle of Ortho Tri-Cyclen (EE 35 μg with NGM 0.18/0.215/0.25 mg) from days 1-28. In period 2, participants received a full cycle of Ortho Tri-Cyclen LO (EE 25 μg with NGM 0.18/0.215/0.25 mg) plus ATV/RTV (300/100 mg once daily) on days 29-42. PK assessments were performed on days 14 and 42 in periods 1 and 2, respectively.

RESULTS

ATV/RTV with dose-normalized EE/NGM resulted in geometric mean reductions of 16% in EE peak plasma concentration (C(max)), 19% in EE area under the concentration-time curve for a dosing interval (AUC([τ])) and 37% in EE lowest plasma concentration (C(min)), compared with EE 35 μg with NGM in the absence of ATV/RTV. NGM with EE and ATV/RTV 300/100 mg once daily resulted in increases of approximately 68%, 85% and 102% in 17-deacetyl NGM C(max), AUC((τ)) and C(min), respectively. Two participants discontinued the study because of adverse events.

CONCLUSIONS

ATV/RTV with Ortho Tri-Cyclen was well-tolerated and reductions in EE were not predicted to decrease contraceptive efficacy if the formulation contained ≥30 μg of EE.

摘要

背景

口服避孕药与蛋白酶抑制剂同时服用会因药物相互作用而变得复杂。一项开放标签的三阶段单序列研究评估了阿扎那韦（ATV）/利托那韦（RTV）与复方口服避孕药（Ortho Tri-Cyclen®）以及与复方口服避孕药低剂量片（Ortho Tri-Cyclen® LO，美国新泽西州拉里坦市奥索-麦克尼尔-杨森制药公司）同时服用对炔雌醇（EE）、诺孕酯（NGM）、ATV和RTV药代动力学（PK）的影响。

方法

共有20名年龄在18至45岁的健康女性接受了研究治疗。在导入期和第1阶段，参与者在第1至28天接受一个完整周期的复方口服避孕药（EE 35μg与NGM 0.18/0.215/0.25mg）。在第2阶段，参与者在第29至42天接受一个完整周期的复方口服避孕药低剂量片（EE 25μg与NGM 0.18/0.215/0.25mg）加ATV/RTV（300/100mg每日一次）。分别在第1阶段和第2阶段的第14天和第42天进行PK评估。

结果

与不使用ATV/RTV时的EE 35μg与NGM相比，ATV/RTV与剂量标准化的EE/NGM导致EE血浆峰浓度（C(max)）几何平均降低16%，给药间隔的浓度-时间曲线下面积（AUC([τ])）降低19%，EE最低血浆浓度（C(min)）降低37%。EE与NGM以及每日一次的ATV/RTV 300/100mg导致17-去乙酰诺孕酯的C(max)、AUC((τ))和C(min)分别增加约68%、85%和102%。两名参与者因不良事件退出研究。