Comparative Bioavailability of Papaverine Hydrochloride, Papaverine Hexametaphosphate and Papaverine Polymetaphosphate

Abstract

Papaverine hexametaphosphate and papaverine polymetaphosphate salts were Prepared and isolated. Experiments were conducted in mongrel dogs to compare the bioavailability of papaverine hydro-chloride, papaverine hexametaphosphate and papaverine polymeta-phosphate. The metaphosphates resulted in greater area under the curve compared to the hydrochloride salt, however, there was no difference observed in the lag time, apparent absorption rate constant, time of peak or maximum plasma concentrations obtained by any of the three salts. Intravenous doses of papaverine hydrochloride were given to all dogs to determine the absolute bioavailability. The pharmacokinetic parameters and first order transfer constants for drug disposition were calculated from the intravenous data; whereas, the apparent absorption rate constant was estimated from percent unabsorbed versus time plots. The pharmacokinetic analysis confirm a three compartment model for the drug in the mongrel dog.