[Metabolism and pharmacokinetics of piprozoline in the rat, dog and man. 1. Studies with the radioactively-labeled substance].

The new choleretic ethyl (Z-3-ethyl-4-oxo-5-piperidino-thiazolidin-2-ylidene) acetate (piprozoline, Gö 919, Probilin) is absorbed well and rapidly in rats, dogs and humans. Maximum 14C plasma concentrations are found 1-2 h after oral administration of the labelled substance to fasting animals and human volunteers. When administered to test persons after breakfast, the absorption is delayed but the absorbed amount is unaffected. Elimination of the radioactivity from the plasma occurs in two phases; 24 h after administration the radioactivity concentration has dropped to 5-8% of the maximum levels. Piprozoline is almost completely metabolized during absorption. The primary metabolic step is the enzymatic hydrolysis of the ester bond to the corresponding acid (metabolite I). At the time of maximum plasma concentration most of the plasma radioactivity corresponds to metabolite I, which also possesses choleretic activity. Approx. 65% of the radioactive dose is eliminated renally in all three species, approx. 60% being excreted within the first 24 h. Approx. 40-60% of the urinary radioactivity can be ascribed to metabolite I, both in its free form and conjugated with glucuronic acid. No unchanged substance is found in the urine. A comparison of the pharmacokinetic and metabolic behaviour of piprozoline in rats, dogs and humans showed that it was similar in all three species.