Comparative study of acetaminophen disposition in sheep at three developmental stages: the fetal, neonatal and adult periods.

The disposition of acetaminophen was studied in adult nonpregnant ewes, neonatal lambs, pregnant ewes and their fetal lambs following single intravenous bolus doses. Comparisons of the pharmacokinetic parameters of acetaminophen were made between sheep at different developmental periods to examine the developmental alteration in the physiological and biochemical processes governing drug disposition. The four groups of animals exhibited distinct and significant differences in the total clearance and metabolic clearances of acetaminophen and the renal clearances of the glucuronide and sulfate conjugates. Placental transfer of acetaminophen from fetus to mother serves as the dominant route of fetal removal or clearance of the drug.