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Pharmacokinetics of captopril in dogs and monkeys.

[14C]Captopril was given as a priming dose, followed by constant intravenous infusion for 4 or 6 hr, to three anesthetized dogs and three anesthetized monkeys. Blood, urine, and bile samples were collected during and after drug infusion. Pharmacokinetic evaluations were carried out exclusively on data obtained for unchanged captopril. The average total body clearance (ClT) and the renal clearance (ClR) of captopril, in milliliters per kilogram per hour, were 605 and 341 in the dog and 1135 and 944 in the monkey. The biliary clearance of captopril was negligible in both species. The greater difference between the ClR and ClT values in the dog compared to that in the monkey was the result of more extensive metabolism of captopril by the dog. Since almost all of the radioactive dose was recovered in urine in both species, captopril and its metabolites were almost exclusively eliminated by the kidneys. One primary reason that body and renal clearance values of captopril were much greater in the monkey than in the dog was that the net tubular secretion fo captopril was about three times greater in the monkey (82%) than in the dog (28%). The volume of distribution of captopril was higher in the monkey (3.6 liters/kg) than in the dog (2.6 liters/kg); the volume of the central compartment was about the same (0.5 liter/kg) for both species. The terminal half-life value was slightly higher in the dog (2.8 hr) than in the monkey (2.2 hr).