Concurrent determination of hepatic bioavailability of salicylamide by three techniques in the dog

Three methods of measuring hepatic first-pass metabolism of salicylamide in dogs that had undergone portacaval transposition were compared. The drug in both its radiolabeled (0.74 MBq) and unlabeled (20 mg/kg) forms was infused concurrently into forelimb and hindlimb veins, respectively. Because of the transposition, drug from the hindlimb is subject to first-pass metabolism in the liver. Bioavailability is a complementary measure of the extent of this metabolism. The three methods of determining bioavailability were continuous withdrawal of blood to determine the ratio of the areas under the plasma concentration versus time curves, ratio of specific activities in plasma after all the drug had been administered, and the conventional method, measurement of the ratio of areas determined from sequential plasma concentrations. The three techniques were found to give virtually identical values for bioavailability. Each method has its own advantages, limitations, and possible applications. The continuous withdrawal technique is potentially most applicable for drugs with short half-lives. The ratio of specific activities may be the preferred method for drugs with long half-lives. The conventional method is limited by the number of samples needed, but is potentially useful under those conditions in which data following test and intravenous routes of administration are available.