Vol. 274, Issue 5, E791-E795, May 1998
Effect of pregnancy on the metabolic clearance rate and the
volume of distribution of oxytocin in the baboon
Wlodzimierz B.
Kowalski1,
Lubomir
Diveky1,
Ramkrishna
Mehendale1,
Michael
Parsons2, and
Laird
Wilson Jr.1
1 Departments of Obstetrics and
Gynecology, University of Illinois at Chicago, Chicago, Illinois
60612; and 2 University of South
Florida, Tampa, Florida 33606
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 · kg1
in pregnancy and 16.3 ± 1.4 ml · min1 · kg1
postpartum (P < 0.05), respectively,
and 23.7 ± 2.8 vs. 16.9 ± 3.7 ml · min1 · kg1
(P < 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 > 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 < 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.
metabolism; volume of distribution; pharmacokinetics
