Aim: This study investigated the pharmacokinetics of prucalopride in Chinese healthy volunteers.
Methods: This single-center, open-label study was conducted in 14 healthy males and 14 healthy females, aged 18 - 45 years. Fasted subjects received a single dose of 2 mg prucalopride, and after a 7-day wash-out period, they received the same dose once-daily for 7 days at fasted condition. Serial blood samples were taken at predefined time-points to measure plasma concentrations of prucalopride during the single-dose and multi-dose period. Daily evaluations were made on defecation frequency and stool consistency. Safety assessments were performed throughout the study.
Results: After oral administration, prucalopride reached the peak plasma level (Cmax) of 4.92 ± 0.78 ng/ml with a median time to Cmax (tmax) of 2 hours and resulted in an area under concentration-time curve (AUC0-∞) of 89.3 ± 15.82 h×ng/ml. Steady state was attained 3 days after repeated dosing, when Cmax was 8.09 ± 1.21 ng/ml and AUC0-24h was 103.6 ± 14.35 h×ng/ml. Pharmacokinetic profiles were similar between genders except males had a slightly lower exposure level. Marked increase of defecation frequencies and predominance of "watery" or "loose" stools were seen after a single dose. The responses during multi-dose period were less remarkable and returned to baseline in 3 days.
Conclusion: The pharmacokinetics of prucalopride 2 mg oral dose in Chinese healthy volunteers are similar to those observed in Caucasians. Compared to females, males exhibited a slightly lower exposure of prucalopride but similar changes of bowel habits were observed in both genders suggesting the inter-gender pharmacokinetic differences are not clinically relevant.