EFFECT OF RITONAVIR ON THE PHARMACOKINETICS OF ETHINYL ESTRADIOL IN HEALTHY FEMALE VOLUNTEERS

Aims To assess the effects of the protease inhibitor ritonavir on the pharmacokinetics of ethinyl oestradiol in healthy female volunteers. M ethods This was an open-label, single centre study in 23 subjects who received two single doses of oral contraceptive containing 50 mu g eth inyl oestradiol on Day 1 (alone) and on Day 29 during concomitant rito navir. Each subject received 16 days of every 12 h doses of ritonavir from Day 15 through Day 30. Blood samples were collected for serum eth inyl oestradiol concentrations for 48 h after each dose and for plasma ritonavir on Day 29 at 0 and 4 h postdose. Results Statistically sign ificant decreases in ethinyl oestradiol mean C-max (-32%) and mean AUC (-41%), and a statistically significant increase in the mean terminal elimination rats constant (+31%) were observed during concomitant rit onavir. The harmonic mean terminal half-life decreased from 17 h to 13 h during concomitant ritonavir. No statistically significant change w as 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), respe ctively. The changes in ethinyl oestradiol pharmacokinetics were consi stent with an increase in clearance from enzymatic induction of glucur onidation and/or cytochrome P450 hydroxylation. Mean steady-state rito navir concentrations of 6.5 and 13.4 mu g ml(-1) were observed at 0 an d 4 h postdose, respectively. Conclusions Considering the extent of th e decrease in ethinyl oestradiol concentrations, the use of alternate contraceptive measures should be considered when ritonavir is being ad ministered.