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.

Key words::

• Bioavailability
• Bioequivalence
• Gastroesophageal reflux disease
• Mosapride
• Rabeprazole

Transparency

Declaration of funding

This study was sponsored by Laboratorios Phoenix S.A.I.C. y F. Buenos Aires, Argentina.

Declaration of financial/other relationships

The authors have indicated that they have no conflicts of interest regarding the content of this article and have received no payment in preparation of this manuscript. G.A.K., P.C., R.B., and G.D.G. have disclosed that they are affiliated with Second Chair of Pharmacology, School of Medicine, Universidad de Buenos Aires. A.R.A. is a staff member at Laboratorios Phoenix S.A.I.C. y F.; F.d.M. and M.V.S. that they are affiliated with IACA Laboratorios.

CMRO peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

The authors thank R.A. Diez, Second Chair of Pharmacology, School of Medicine, Universidad de Buenos Aires for revision of the manuscript.

Notes

* Rabec Plus, Mosar and Rabec are registered trade names of Laboratorios Phoenix S.A.I.C. y F., Buenos Aires, Argentina.