[Studies on the pharmacokinetics and biotransformation of ipratropium bromide in the rat and dog].

The pharmacokinetics of the bronchodilator (8r)-3alpha-hydroxy-8-isopropyl-1alphaH,5alphaH-tropanium-bromide-(+/-)-tropate (ipratropiumbromide, Sch 1000, Atrovent) were studied in the rat and the dog after administering radioactive material (14C). The blood level of Sch 1000 following oral dosing showed plateaus in both the rat and the dog over a period of 2--8 h following administration. Subsequent elimination from the blood occurs with a half-life of 7h (rat) and 10 (dog). The half-life of elimination following i.v. administration is 1.9 h (rat) and 3.4 h (dog). In the rat biliary excretion occurs to the extent of 3.2% following oral dosing and 17.7% following i.v. application. In the same species renal excretion is 5.5% following oral administration and 58% following i.v. administration. Renal excretion in the dog, on the other hand, averaged 28% following oral and 55% following i.v. dosing, respectively. On the basis of a comparison of the areas under the blood level curves and also from the renal excretion following oral and i.v. dosing, i.e. disregarding absorption by gastrointestinal tissue, absorption was calculated as being 12% in the rat and 38% in the dog. Absorption in the rat after 1--3 h was calculated at 17--35% including the gastrointestinal tissue. Four metabolites and the unchanged substance could be detected in the 8-h urine of the rat. In the urine of the dog, the percentage of unchanged substance fell from a maximum of 81% (after 1 h) to 20% (after 47 h) in terms of radioactivity in the urine.