The pharmacokinetics of salicylate in the pregnant Wistar rat.
Sodium salicylate, in a single dose of 50 mg/kg, was administered by iv injection to nonpregnant female and 20-day pregnant Wistar rats. Blood samples (for serum) and urine were collected and analyzed for salicylate, gentisic acid, salicyluric acid, and salicyl glucuronides by HPLC. Pregnant rats showed a significant decrease in body weight-normalized total clearance but no change in absolute total clearance of salicylate. On a body weight-adjusted basis there was a slight increase in the apparent volume of salicylate distribution in pregnancy but this increase becomes highly significant if expressed in absolute terms. The biological half-life of salicylate was significantly increased in late pregnancy. Serum protein binding of salicylate is decreased in pregnancy relative to nonpregnant females but in both groups binding shows a concentration dependence. The partial clearances of both salicyluric and gentisic acids were reduced by pregnancy in the rat whereas that of the salicyl glucuronides appeared unchanged. This latter result in intact pregnant animals contrasts with previously reported decreases in glucuronyltransferase activity in isolated liver preparations from pregnant rats.
Dean
M
M
Department of Paediatrics, University of Adelaide, Australia.
Penglis
S
S
Stock
B
B
D000818:Animals; D005260:Female; D005965:Glucuronates / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D051381:Rats; D012459:Salicylates / Q000493:pharmacokinetics*
D005965:Glucuronates; D012459:Salicylates