Prodrug approach of orotic acid using an absorption model

Abstract A series of ester prodrugs of orotic acid were synthesized. Using in vitro methods, in particular, an absorption model system, the n -butyl ester of orotic acid was found to be the ester prodrug with optimal physicochemical properties. Pharmacokinetic studies on rabbits confirmed these results. The bioavailability of orotic acid after oral administration of the n -butyl ester prodrug was found to be 3.4-times higher as compared to the methylglucamine salt of orotic acid. A similar increase in bioavailability was predicted based on the in vitro half life for transport in the absorption model.