[Biochemical studies with oxitropium bromide. 1. Pharmacokinetics and metabolism in the rat and dog]

The bronchospasmolytic drug (8r)-6 beta, 7 beta-epoxy-8-ethyl-3 alpha-[(-)-tropoyloxy]-1 alpha H, 5 alpha H-tropanium bromide (oxitropium bromide, Ba 253 BR, Ventilat) was tested pharmacokinetically as a 14C labelled substance in rats and dogs. Following oral administration low concentrations of radioactivity persisting over several hours were measured in the blood of dogs and rats. The active ingredient which can be separated from the metabolites by thin layer chromatography and quantified via the radioactivity reaches a maximum in the rat plasma after 1 to 2 h; it is then eliminated from the blood with a half-life of approx. 4 h. Following intravenous administration the radioactivity measured directly (active ingredient + metabolites) is distributed rapidly into the tissue of the rat and the dog. The distribution phase is followed by a relatively fast elimination phase ending in the terminal elimination phase approx. 1 h after administration. Rats and dogs eliminate the radioactivity mainly with the feces after oral administration, whereas following intravenous administration the rat eliminates about half with the feces and half via the kidneys. Biliary excretion of the rat is 12% after oral and 14% after intravenous administration. The rat absorbs 14% and the dog 28% of dose. Five metabolites have been demonstrated in the urine of the rat and the dog. Metabolism takes place exclusively in the tropaic acid part of the molecule and by hydrolysis of the compound.