Effect of ritonavir on the pharmacokinetics of ethinyl oestradiol in healthy female volunteers
Ouellet, D.; Hsu, A.; Qian, J.; Locke, C.S.; Eason, C.J.; Cavanaugh, J.H.; Leonard, J.M.; Granneman, G.R.
British Journal of Clinical Pharmacology 46(2): 111-116
1998
ISSN/ISBN: 0306-5251 PMID: 9723818 DOI: 10.1046/j.1365-2125.1998.00749.xDocument Number: 275589
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 mug 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 Cmax (-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 tmax. The ratios of means (95% confidence intervals) for Cmax 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 mug 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.