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 14C-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 14C pharmacokinetics and excretion. The oral 14C-dose was rapidly and almost completely absorbed from the duodenum and small intestine within 30 min in the male rat and 14C 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 Cmax of 14C, whereas there was some such evidence for AUG24. Tissue 14C 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, 14C concentrations in most tissues were similar to, or lower than, those in the plasma. The extent of placental transfer of 14C was small and less than 0.09% of a maternal dose reached a foetus. 14C diffused into maternal milk at concentrations similar to those in the plasma. The 14C-dose was rapidly excreted in male rats, mostly in the urine (about 80%) during 6 h post dose. Recoveries of 14C in mass balance (excretion) studies were in the range 96-100%. There were no apparent gender differences in the disposition of 14C-pilocarpine in the rat.
Omori
Yasuhiro
Y
Clinical Development, Kissei Pharmaceutical Co., Ltd., Nagano, Japan.
Endo
Takuro
T
Hara
Yoshiki
Y
Nishiyama
Masahiko
M
Midgley
Ian
I
Smart
Clair I
CI
John
Alexandra J
AJ
Chasseaud
Leslie F
LF
McBurney
Alan
A
John
Brian A
BA
D000284:Administration, Oral; D000818:Animals; D001646:Bile / Q000378:metabolism; D005260:Female; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008297:Male; D008431:Maternal-Fetal Exchange; D008892:Milk / Q000378:metabolism; D018721:Muscarinic Agonists / Q000493:pharmacokinetics*; D010862:Pilocarpine / Q000493:pharmacokinetics*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D018721:Muscarinic Agonists; D010862:Pilocarpine