title: Relative bioavailability of a 5 mg mosapride/10 mg rabeprazole fixed dose combination tablet versus separate single tablets in healthy volunteers: a single-dose randomized open-label crossover study.
abstract: OBJECTIVE
  To evaluate the relative bioavailability of a new formulation containing 5 mg mosapride and 10 mg rabeprazole (T) and compare it with the branded formulations of both drugs co-administered in separate tablets (R) to meet the regulatory requirements of bioequivalence in Argentina.
  
  
  METHODS
  A randomized-sequence, open-label, two-period crossover study was conducted on 24 healthy Caucasian volunteers in a fasting state. A single oral dose of either T or R formulations was followed by a 7-day washout period. Blood samples for mosapride were collected before administration (baseline) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, and 24 h after administration. Samples for rabeprazole were taken baseline and at 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8 and 10 h after dosing. Mosapride and rabeprazole concentrations were determined using a validated LC-MS/MS method. Adverse events were monitored based on clinical parameters and volunteer reports.
  
  
  RESULTS
  The geometric means (90% CI) C(max) for mosapride in T and R were 23.13 (20.05-39.45) and 23.09 (21.69-32.37) ng/mL, the AUC(0-)(t) were 70.80 (66.23-102.37) and 70.81 (66.35-93.26) ng h/mL and the AUC(0-∞) were 74.05 (69.29-106.11) and 74.98 (70.43-97.77) ng h/mL. For rabeprazole T and R the C(max) were 197.42 (186.12-239.91) and 195.50 (186.08-250.07) ng/mL, the AUC(0-)(t) were 294.90 (275.13-374.15) and 296.96 (280.11-387.89) ng h/mL and the AUC(0-∞) were 301.12 (280.78-380.82) and 304.07 (286.60-394.21), respectively. No differences were detected between the formulations. The T/R ratios (90% CI) for C(max), AUC(0-)(t) and AUC(0-∞) were 100.17% (82.35-121.84), 99.99% (87.58-114.16) and 98.77% (87.02-112.11) for mosapride, and 100.99% (85.14-119.77), 99.31% (84.74-116.38) and 99.03% (85.07-115.28) for rabeprazole. No subject complained of adverse events.
  
  
  CONCLUSIONS
  In this single-dose study, the mosapride/rabeprazole tablets (test formulation) met the criterion for bioequivalence with the reference formulations. Study limitations include single-dose, open-label design, and a small sample of healthy volunteers.
authors.affiliation: Department of Pharmacology, School of Medicine, Universidad de Buenos Aires, Argentina.
authors.forename: G A
authors.initials: GA
authors.lastname: Keller
authors.forename: P
authors.initials: P
authors.lastname: Czerniuk
authors.forename: R
authors.initials: R
authors.lastname: Bertuola
authors.forename: F
authors.initials: F
authors.lastname: de Mena
authors.forename: M V
authors.initials: MV
authors.lastname: Simoni
authors.forename: A R
authors.initials: AR
authors.lastname: Assefi
authors.forename: Guillermo
authors.initials: G
authors.lastname: Di Girolamo
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D001549:Benzamides / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D018592:Cross-Over Studies; D004338:Drug Combinations; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D064750:Rabeprazole; D013607:Tablets; D053719:Tandem Mass Spectrometry / Q000379:methods; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001549:Benzamides; D004338:Drug Combinations; D005765:Gastrointestinal Agents; D009025:Morpholines; D013607:Tablets; D064750:Rabeprazole; C062720:mosapride