Effect of ritonavir on the pharmacokinetics of ethinyl oestradiol in healthy female volunteers期刊界 All Journals 搜尽天下杂志传播学术成果专业期刊搜索期刊信息化学术搜索

Effect of ritonavir on the pharmacokinetics of ethinyl oestradiol in healthy female volunteers

Authors:	Daniele Ouellet,Ann Hsu,Jiang Qian,Charles S. Locke,Carolyn J. Eason,John H. Cavanaugh,John M. Leonard,& G. Richard Granneman

Affiliation:	Abbott Laboratories, Abbott Park, IL, 60064–3500, U.S.A

Abstract:	Aims To assess the effects of the protease inhibitor ritonavir on the pharmacokinetics of ethinyl oestradiol in healthy female volunteers. Methods This was an open-label, single centre study in 23 subjects who received two single doses of oral contraceptive containing 50 μg ethinyl oestradiol on Day 1 (alone) and on Day 29 during concomitant ritonavir. Each subject received 16 days of every 12 h doses of ritonavir from Day 15 through Day 30. Blood samples were collected for serum ethinyl oestradiol concentrations for 48 h after each dose and for plasma ritonavir on Day 29 at 0 and 4 h postdose. Results Statistically significant decreases in ethinyl oestradiol mean C _max (−32%) and mean AUC (−41%), and a statistically significant increase in the mean terminal elimination rate constant (+31%) were observed during concomitant ritonavir. The harmonic mean terminal half-life decreased from 17 h to 13 h during concomitant ritonavir. No statistically significant change was noted in t _max. The ratios of means (95% confidence intervals) for C _max and AUC were 0.682 (0.612–0.758) and 0.595 (0.506–0.694), respectively. The changes in ethinyl oestradiol pharmacokinetics were consistent with an increase in clearance from enzymatic induction of glucuronidation and/or cytochrome P450 hydroxylation. Mean steady-state ritonavir concentrations of 6.5 and 13.4 μg ml⁻¹ were observed at 0 and 4 h postdose, respectively. Conclusions Considering the extent of the decrease in ethinyl oestradiol concentrations, the use of alternate contraceptive measures should be considered when ritonavir is being administered.

Keywords:	ritonavir protease inhibitor ethinyl oestradiol pharmacokinetics induction glucuronidation drug interaction oral contraceptive

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