title: Pharmacokinetics of single and repeated oral doses prucalopride in healthy Chinese volunteers.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Phase I Unit, Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Beijing, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Chen
authors.forename: Ji
authors.initials: J
authors.lastname: Jiang
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Hongzhong
authors.initials: H
authors.lastname: Liu
authors.forename: Wen
authors.initials: W
authors.lastname: Zhong
authors.forename: Pei
authors.initials: P
authors.lastname: Hu
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D044466:Asian People; D001572:Benzofurans / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D002681:China; D003672:Defecation / Q000187:drug effects*; D004334:Drug Administration Schedule; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D058828:Serotonin 5-HT4 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D012737:Sex Factors; D013607:Tablets; D055815:Young Adult
chemical_list: D001572:Benzofurans; D005765:Gastrointestinal Agents; D058828:Serotonin 5-HT4 Receptor Agonists; D013607:Tablets; C406662:prucalopride