The pharmacokinetics and protein binding of disopyramide in pigs

The pharmacokinetics of disopyramide were investigated in 5 pigs. Disopyramide was administered as intravenous bolus injections at different doses and as intravenous infusions at different rates. By measuring the free and total concentrations in plasma of parent compound and desisopropyldisopyramide (the main metabolite in humans) and the amounts excreted in urine it was found that disopyramide had a concentration dependent protein binding and that free and total concentrations could be described by a two-compartment model with a t1/2, beta of approximately 2 hours. The free concentrations were found to be more valuable for estimating the kinetic parameters. The total clearance of disopyramide in the pig was found to approximately 3 ml/min./kg which is about 3 times greater than in man. In contrast to humans the free clearance in the pig increased with declining concentration. Apart from this the kinetics of disopyramide in the pig were very similar to those in man. In conclusion the pig could be a relevant model for studying the pharmacokinetics in humans.