Absorption, distribution and excretion of 14C-pilocarpine following oral administration to rats

The absorption, distribution and excretion of pilocarpine (CAS 92-13-7) were studied after single oral doses of C-14-pilocarpine hydrochloride (CAS 54-71-7) to the Sprague-Dawley rat, administered in aqueous solution mainly at a dose level of 0.3 mg/kg. Rats also received single intravenous doses at 0.3 mg/kg so as to compare C-14 pharmacokinetics and excretion. The oral C-14-dose was rapidly and almost completely absorbed from the duodenum and small intestine within 30 min in the male rat and C-14 concentrations in plasma declined biexponentially with a terminal half-life of about 9 h. Over the oral dosage range studied, i.e. 0.1-1.0 mg/kg, there was no evidence of significant non-proportionality for C-max of C-14, whereas there was some such evidence for AUC(24). Tissue C-14 concentrations in male and pregnant female (Day 18) rats peaked at 0.5 h and mostly declined in parallel with those in the plasma. Excluding tissues concerned with drug absorption and elimination, C-14 concentrations in most tissues were similar to, or lower than, those in the plasma. The extent of placental transfer of C-14 was small and less than 0.09% of a maternal dose reached a foetus. C-14 diffused into maternal milk at concentrations similar to those in the plasma. The C-14-dose was rapidly excreted in male rats, mostly in the urine (about 80%) during 6 h post dose. Recoveries of C-14 in mass balance (excretion) studies were in the range 96-100%. There were no apparent gender differences in the disposition of C-14-pilocarpine in the rat.