DIFFERENCES IN THE ORAL BIOAVAILABILITY OF 3 RAFOXANIDE FORMULATIONS IN SHEEP

The bioavailability of a modified rafoxanide oral suspension was compa red to the original innovator product and a generic formulation in a s ingle dose, randomised, parallel design study in sheep (n=30). The are a under rafoxanide plasma concentration versus time curve (AUC), AUC e xtrapolated to infinity, and maximum plasma rafoxanide concentrations (Cmax), were used to compare the extent of absorption of the formulati ons. All 3 parameters were significantly (p <0,01) smaller for both th e modified and generic formulations relative to the original product. There were no significant (p >0,05) differences between the modified a nd generic formulations. The mean point ratio % of the modified to ori ginal and modified to generic formulations for the 3 parameters were 3 6,4% 35%, 45,9% and 70,9%, 70, 79,7% respectively. In terms of the cal culated 90% confidence t-intervals of the mean % ratios, the modified and generic formulations were not bioequivalent to the original produc t, 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 b efore absorption of rafoxanide for all formulations, of c 5 h was obse rved. The differences in oral bioavailability or rafoxanide and relate d anthelmintic formulations have implications for the efficacy and reg istration of generic products.