On day 5 of the oral contraceptive plus prucalopride period, one participant had pre-dose concentrations of prucalopride, ethinylestradiol, and norethisterone that were much lower than would be theoretically expected and much lower than the pre-dose concentrations measured on other days of the same treatment period in this participant. On day 3 this individual had reported nausea and vomiting, and on days 3 and 4 she had not reported intake of trial medication in her participant diary (although later she stated that she had taken the trial medication). After supervised drug intake on day 5, drug absorption GNS-1480 mouse appeared

normal (as evidenced by the ethinylestradiol and norethisterone selleck compound profiles on day 5, and the day 6 prucalopride pre-dose and 24-hour post-dose concentrations), which strongly learn more suggests that this individual did not take the study medication on days 3 and/or 4. Therefore, statistical comparison of the day 5 pharmacokinetic parameters was also performed on a subset of 12 participants, excluding this suspected non-compliant participant. 3.2 Ethinylestradiol Pharmacokinetics On day 1, Cmax was reached at a median time of 1 hour after dosing with both treatments (Fig. 2 and Table 1). There were no statistically significant differences in

Cmax, tmax, or AUC24 between treatments (oral contraceptive vs. oral contraceptive plus prucalopride; Table 1). The geometric mean treatment ratios for Cmax and AUC24 were 110.37 % and 95.52 %, respectively, and the associated 90 % CIs were within the predefined equivalence limits of 80–125 % (Table 1). Fig. 2 Mean ethinylestradiol plasma concentration–time profiles on day 1 and day 5 (n = 13). OC oral contraceptive Table 1 Pharmacokinetic parameters and summary of the equivalence analysis for ethinylestradiol Parameter Treatment A Treatment B OC + prucalopride

enough versus OC alone OC alonea OC + prucalopridea PE (%) 90 % CI p value Day 1 (n = 13)  tmax (h) 1.0 [1.0–2.0] 1.0 [1.0–2.0] 0.00 −0.50, 0.00 0.4224  Cmax (pg/mL) 90.5 ± 21.8 103 ± 32.0 110.37 99.74, 122.13 0.1079  AUC24 (pg·h/mL) 727 ± 156 720 ± 204 95.52 90.70, 100.61 0.1409 Day 5 (n = 13)b  tmax (h) 1.0 [1.0–3.0] 1.0 [1.0–3.0] −0.50 −1.00, 0.00 0.0644  Cmin (pg/mL) 18.6 ± 7.4 17.8 ± 8.1 83.00 65.43, 105.29 0.1872  Cmax (pg/mL) 130 ± 34 123 ± 27 96.07 89.37, 103.28 0.3412  AUCτ (pg·h/mL) 1,153 ± 323 1,090 ± 296 92.54 85.07, 100.66 0.1260  t½ (h) 17.1 ± 2.4 15.0 ± 3.2 – – 0.0154 Day 5 (n = 12)b  tmax (h) 1.0 [1.0–3.0] 1.0 [1.0–3.0] −0.25 −0.50, 0.00 0.1530  Cmin (pg/mL) 19.4 ± 7.0 19.3 ± 6.3 97.10 86.83, 108.59 0.6438  Cmax (pg/mL) 132 ± 35 126 ± 27 99.12 92.80, 105.88 0.8140  AUCτ (pg·h/mL) 1,135 ± 331 1,119 ± 288 97.65 93.36, 102.14 0.3605  t½ (h) 17.4 ± 2.2 15.3 ± 3.1 – – 0.