Urinary pharmacokinetics of physostigmine in the rat.

Abstract

Urinary pharmacokinetics of 3H-Physostigmine (Phy) were studied in rat after an intramuscular administration of 650 micrograms/kg. Urine was collected at 0-1, 1-2, 2-4, 4-6, and 6-24 hr and every 24 hr for seven days. The rats were sacrificed by decapitation and the tissues were analyzed for radioactivity. Less than one percent (.87%) of the dose remained in tissues after the seventh day. Liver, followed by kidney, accounted for the highest activity compared to other tissues. The amounts of 3H-Phy and metabolites were determined by HPLC and the rapid decline of Phy in urine was observed. Most of the radioactivity found in the urine was due to metabolites (47% of dose in 24 hr) indicating extensive metabolism. The cumulative percent of radioactivity excreted in the urine was 30.3 +/- 12.6% in 6 hr, 44.4 +/- 13.1% in 24 hr which increased to 52.7 +/- 12.0% after seven days. Urinary elimination rate constant (Ku) of Phy was found to be .051 +/- .009 hr-1 indicating that the urinary elimination of Phy accounted for a minor part (2.5-4.%) of the systemic elimination.