Comparative distribution and embryotoxicity of acetylsalicylic acid in pregnant rats and rhesus monkeys.

Acetylsalicylic acid was given orally to pregnant rats on gestation Days 9–12 and to pregnant monkeys on Days 23–32 and to nonpregnant females of both species at doses of 100 and 150 mg/kg twice daily. Concentrations of salicylic acid were determined in maternal plasma, embryo, decidua, placenta, and chorionic and amniotic fluids at 1, 2, 4, 8, and 17 hr after the last dosage. Total salicylic acid concentrations in plasma after comparable doses were generally higher in rats than in monkeys and in nonpregnant than in pregnant rats, but concentrations varied in pregnant vs nonpregnant monkeys. Unbound salicylate in rat plasma ranged between 30 and 50% of the total plasma concentration and was closely paralleled by the concentration in the rat embryo. Unbound salicylate in monkey plasma was lower, ranging between 17 and 30% of the total plasma concentration and was to some degree paralleled by the concentration in the monkey embryo. The greater embryotoxicity of acetylsalicylic acid in the rat than in the monkey was correlated with higher concentrations and longer duration of concentrations in the respective embryos on a day-to-day basis.