Differences in the oral bioavailability of three rafoxanide formulations in sheep.

G E Swan, C J Botha, J H Taylor, M S Mülders, P P Minnaar, A Kloeck

Index: J. S. Afr. Vet. Assoc. 66(4) , 197-201, (1995)

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Abstract

The bioavailability of a modified rafoxanide oral suspension was compared to the original innovator product and a generic formulation in a single dose, randomised, parallel design study in sheep (n = 30). The area under the rafoxanide plasma concentration versus time curve (AUC), AUC extrapolated to infinity, and maximum plasma rafoxanide concentrations (Cmax), were used to compare the extent of absorption of the formulations. All 3 parameters were significantly (p < or = 0.01) smaller for both the modified and generic formulations relative to the original product. There were no significant (p > 0.05) differences between the modified and generic formulations. The mean point ratio % of the modified to original and modified to generic formulations for the 3 parameters were 36.4%, 35%, 45.9% and 70.9%, 70%, 79.7%, respectively. In terms of the calculated 90% confidence t-intervals of the mean % ratios, the modified and generic formulations were not bioequivalent to the original product, since they were substantially below the accepted range of 80-125%. No significant differences (p > 0.05) were noted for the time to Cmax and Cmax/AUC, both measurements of rate of absorption. A lag period before absorption of rafoxanide for all formulations of c 5 h was observed. The differences in oral bioavailability of rafoxanide and related anthelmintic formulations have implications for the efficacy and registration of generic products.