Absorption, distribution and excretion of 14C-pirenzepine in rats. Accumulation characteristics after multiple dose regimen.

Absorption, distribution and excretion of 14C-labelled 5,11-dihydro-11-[(4-methyl-1-piperazinyl) acetyl]-6H-pyrido[2,3-b][1,4]-benzodiazepin-6-one-dihydrochloride (pirenzepine, LS-519 Cl2) were studied in SD-JCL rats. After a single i.v. injection of the drug (2 mg/kg), the concentration of radioactivity in the blood decreased bi-phasically with half-lives of 1 and 8 h. After s.c. administration of the same dose, the drug was very rapidly absorbed and it was shown that the concentrations and the elimination pattern were almost identical to that observed following i.v. injection. After oral administration of 20 mg/kg, absorption was relatively slow, taking 3 h to reach Cmax. The concentrations of radioactivity distributed in most tissues reached their maximum 3 h after a single oral administration, well comparable with that in the blood. In the study with multiple administration (5mg/kg once a day up to 14 days), 24 h after withdrawal of 7-day administration, the concentration in the liver, kidneys and testes were two times those at a 1-day administration. This ratio, however, did not increase furthermore over a 10- to 14- day administration period. All tissue levels gradually decreased with time after the final administration. Thus, no specific or considerable accumulation was demonstrated. The drug found excreted into urine was about 46% and into feces about 53% of the administered dose 96 h after i.v. injection. After single oral administration, urinary excretion was found extremely low, i.e., 8%, while 91% was excreted via feces.