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Pharmacokinetics of biliary excretion of physostigmine in rat.

The biliary excretion of Phy and its metabolites was studied in the rat after i.v. administration of 3H-Phy (100 micrograms/kg). About 60% of the radioactivity was excreted in three hours. The unchanged drug was excreted to the extent of about 23% of the dose and the metabolites were excreted as 37% of the dose. The half-life of Phy was found to be 21.6 +/- 1.8 min (mean +/- S.E.) as determined in bile, 52.1 +/- 9.1 min as determined from serum, and the systemic clearance of Phy was .63 +/- 2.6 ml/min. The mean Kel was found to be .012 min-1. The biliary excretion rate constant was determined to be .014 +/- .001 min-1 for total radioactivity and .008 +/- .002 min-1 for Phy. Biliary clearance of Phy was .18 ml/min. The serum to bile ratio of Phy at 15-30 min was 5.11, indicating rapid concentration of Phy in the bile. Phy may stimulate bile flow in the rat, particularly at early times. The mass spectrum of extracted Phy from bile at m/e 275, 218, 175, 161 and 160 confirmed its identify. From these studies it appears that bile is a significant route of excretion of Phy in the rat.