8 %]), nausea (11 events, n = 10 [62.5 %]), vomiting (7 events, n = 6 [37.5 %]), and diarrhea (4 events, n = 4 [25.0 %]). All cases of headache and diarrhea started on day 1, as did eight of the cases of nausea. Five participants experienced vomiting on day 1 (one of whom also experienced vomiting on day 7), and a sixth participant reported vomiting on day 3. Three

of the episodes of vomiting occurred 1.5–3.5 PD0332991 concentration hours post-dose, while the other four episodes occurred 9–21 hours post-dose. The four AEs that were reported in participants receiving oral contraceptive alone were all moderate cases of headache, three of which occurred on day 1 and one that occurred on day 8. One episode of palpitations was reported, but this did not result in drug discontinuation and was not associated with other serious cardiovascular events. No clinically relevant abnormalities or trends were observed in the laboratory data, vital signs, ECGs, or physical examinations. 4 Discussion Prucalopride was developed for the treatment of LDC000067 chronic constipation, which tends to be more common in women than in men. A high proportion of patients taking prucalopride are therefore

also likely to be taking oral contraceptives. Several oral contraceptives (including ethinylestradiol and norethisterone) find more are metabolized by CYP3A4, induction of which can reduce exposure to the components of the oral contraceptives Sulfite dehydrogenase and risk contraceptive failure. Although there is no indication that prucalopride has CYP3A4-inducing properties, and it has a very low potential for enzyme inhibition, the pharmacodynamic properties of prucalopride

may theoretically lead to reduced absorption of concomitantly used drugs. However, the findings of the current study indicate that prucalopride has no clinically relevant effects on the pharmacokinetics of either ethinylestradiol or norethisterone. Single-dose prucalopride had no effect on the rate or extent of ethinylestradiol and norethisterone absorption, despite a number of participants reporting diarrhea on day 1 of treatment. Thus, the faster transit associated with diarrhea and the known prokinetic effects of prucalopride appear not to have been associated with any clinically relevant effects in terms of drug absorption. This suggests that the absorption of oral contraceptives is unaffected by the changes in transit time evoked by prucalopride, and points to the limited importance of enterohepatic circulation (with possible second-pass absorption as a consequence) in the absorption of oral steroids in humans [17]. In addition, prucalopride did not affect the pharmacokinetics of ethinylestradiol and norethisterone once steady-state concentrations of prucalopride and oral contraceptive were achieved, indicating that there was no metabolic interaction of prucalopride with the oral contraceptive constituents.