EFFECT OF PREGNANCY ON THE METABOLIC-CLEARANCE RATE AND THE VOLUME OFDISTRIBUTION OF OXYTOCIN IN THE BABOON

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 ar terial access and a continuous monitoring of uterine contractions duri ng gestation. Two methods of determining OT pharmacokinetics were util ized (bolus injection vs. continuous infusion). The metabolic clearanc e 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 < 0.05), respectively, and 23.7 +/- 2.8 vs. 16.9 +/- 3 .7 ml.min(-1).kg(-1) (P < 0.05), respectively, as determined during th e 1-h infusion trials (n = 4). The initial dilution volume and the vol ume of distribution at steady state of OT after administration did not differ between pregnant and postpartum animals (P > 0.05). The mean r esidence time (MRT) of OT was shorter during pregnancy, 7.7 +/- 0.8 vs . 10.8 +/- 1.2 min postpartum (P < 0.05). In summary, OT metabolism du ring pregnancy in the baboon is characterized by I) increased clearanc e rate (1.4-fold), 2) accelerated turnover due to the shorter MRT, and 3) unaltered distribution.