Pharmacokinetics of Sch 34343 in rats and dogs

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Abstract
The pharmacokinetics of 14 C-Sch 34343 were studied in rats and dogs following intravenous and intramuscular dosing. In both species, it was rapidly absorbed after intramuscular dosing. The serum AUC for total radioactivity and for intact drug after intramuscular dosing were similar to those obtained after intravenous dosing. Following both routes of drug administration, the elimination of half-life ( T ½ β ) was 7 mm in rats and 25–32 mm in dogs. Following intravenous dosing of 14 C-Sch 34343 to rats, radioactivity in tissues disappeared rapidly with time indicating no tissue accumulation. Highest concentrations of radioactivity were seen in the kidney. Liver, lung, skin and heart appeared to have concentrations of radioactivity similar to those of blood. Sch 34343 was excreted rapidly and primarily into the urine in both rats and dogs. After either route of dosing, urinary excretion of total radioactivity ranged from 84 to 93% and that of intact Sch 34343 from 41 to 51% of the dose, respectively. In addition, the effect of pretreatment with probenecid on the pharmacokinetics in rats and dogs and in anephric rats were also evaluated Pretreatment with probenecid prolonged the elimination half-life in both rats and dogs. Anephric rats had a longer half-life than normal rats.

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