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 14 C-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 14 C pharmacokinetics and excretion. The oral 14 C-dose was rapidly and almost completely absorbed from the duodenum and small intestine within 30 min in the male rat and 14 C 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 14 C, whereas there was some such evidence for AUC 24 . Tissue 14 C 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, 14 C concentrations in most tissues were similar to, or lower than, those in the plasma. The extent of placental transfer of 14 C was small and less than 0.09 % of a maternal dose reached a foetus. 14 C diffused into maternal milk at concentrations similar to those in the plasma. The 14 C-dose was rapidly excreted in male rats, mostly in the urine (about 80 %) during 6 h post dose. Recoveries of 14 C in mass balance (excretion) studies were in the range 96–100 %. There were no apparent gender differences in the disposition of 14 C-pilocarpine in the rat.