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Pharmacokinetic parameters of oxytocin (OT) metabolism were determined during the last third of pregnancy and again 4-8 wk after delivery in the baboon. Animals were placed on a tether system with venous and arterial access and a continuous monitoring of uterine contractions during gestation. Two methods of determining OT pharmacokinetics were utilized (bolus injection vs. continuous infusion). The metabolic clearance rate of OT as determined during the bolus trials (n = 7) was 22.2 +/- 1.5 ml.min-1.kg-1 in pregnancy and 16.3 +/- 1.4 ml.min-1.kg-1 postpartum (P &lt; 0.05), respectively, and 23.7 +/- 2.8 vs. 16.9 +/- 3.7 ml.min-1.kg-1 (P &lt; 0.05), respectively, as determined during the 1-h infusion trials (n = 4). The initial dilution volume and the volume of distribution at steady state of OT after administration did not differ between pregnant and postpartum animals (P &gt; 0.05). The mean residence time (MRT) of OT was shorter during pregnancy, 7.7 +/- 0.8 vs. 10.8 +/- 1.2 min postpartum (P &lt; 0.05). In summary, OT metabolism during pregnancy in the baboon is characterized by 1) increased clearance rate (1.4-fold), 2) accelerated turnover due to the shorter MRT, and 3) unaltered distribution.

Effect of pregnancy on the metabolic clearance rate and the volume of distribution of oxytocin in the baboon