Effects of calcium entry blocker (nicardipine) tocolysis in rhesus macaques: fetal plasma concentrations and cardiorespiratory changes.
Tocolytic doses of nicardipine, a dihydropyridine calcium entry blocker, were administered to chronically catheterized rhesus monkeys between days 128 and 132 of gestation. During periods of spontaneous uterine contractility, a 500 micrograms nicardipine bolus was injected intravenously, and this was followed by continuous infusion (6 micrograms/kg/min) to the mother for 1 hour. Uterine activity (amniotic fluid pressure) and maternal heart rate and blood pressure were monitored continuously. Paired maternal and fetal blood samples were drawn at frequent intervals to monitor pH, PO2, PCO2, and plasma nicardipine concentrations. Peak maternal nicardipine concentrations ranged from 175 to 865 ng/ml while peak fetal levels ranged from 7 to 35 ng/ml. Fetal heart rate and blood pressure were unaffected. However, fetuses became acidotic (pH 7.26 +/- 0.01 versus 7.33 +/- 0.01) and hypoxemic (PO2 16.0 +/- 3.2 versus 24.5 +/- 2.0 mm Hg) after maternal nicardipine treatment (p less than 0.01). Despite the fact that maternal nicardipine treatment exerted a significant tocolytic effect, the undesirable fetal side effects are of concern and deserve further investigation.
Division of Perinatal Biology, School of Medicine, Loma Linda University, California.
C A
CA
Ducsay
J S
JS
Thompson
A T
AT
Wu
M J
MJ
Novy
D000818:Animals; D005260:Female; D005312:Fetal Blood / Q000032:analysis*; D005333:Fetus / Q000187:drug effects*; D008253:Macaca mulatta; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D009529:Nicardipine / Q000627:therapeutic use / Q000633:toxicity*; D007752:Obstetric Labor, Premature / Q000517:prevention & control*; D011247:Pregnancy; D014590:Uterine Contraction / Q000187:drug effects
D009529:Nicardipine