Journal of Bioequivalence & Bioavailability

Abstract

Evaluation of Frog as an Animal Model to Study the Fraction of Oral Dose Absorbed in Humans

Yerasi N, Vurimindi H and Devarakonda K

To evaluate single pass intestinal perfusion method in frog for the prediction of absorption in man and also to evaluate the predictability of this model to classify drugs correctly under biopharmaceutical classification system (BCS). Single Pass Intestinal Perfusion (SPIP) studies were performed in Frogs of the species Rana tigrina using established method for rats with some modifications. Permeability was determined for each selected drug in 6 frogs and the results were presented as mean ± SD. Effective permeability coefficient (Peff) of 12 drugs was calculated. Permeability assessment of some carrier transported drugs which are also substrates for CYP enzymes was also done. Correlation of frog Peff with fraction of dose absorbed (FA) in man was done. Rank order comparison of permeabilities obtained in this study with two other absorption models (human jejunal perfusion, rat intestinal perfusion) was made. The calculated Peff values correlated well with reported Peff values of probe drugs. Good correlation was found between Peff of humans and frogs (r2=0.942). The permeability classification based on frog intestinal permeability of drugs is in high agreement with previously introduced classification, and all the compounds are placed in correct categories as they belong to. The results of this study provided a basis that, as a permeability model in the early drug discovery stage, the single pass intestinal perfusion frog model can be used for the biopharmaceutics classification system. This model may represent a valuable alternative to the low speed and high cost of conventional animal models (typically rodents) for the assessment of intestinal permeability.