Pharmacokinetics and pharmacodynamics of nifedipine in pregnant sheep.
The calcium channel blocker nifedipine was administered to pregnant sheep by a four-level iv infusion at rates of 1-10 micrograms/kg/min. The maternal and fetal plasma nifedipine concentrations were measured along with maternal and fetal heart rate, blood pressure, pH, and blood gases. The two-compartment maternal pharmacokinetics demonstrated a rapid phase t1/2 of 11 min and a slower phase t 1/2 of 137 min. The drug reached the fetus via a first-order process with a t 1/2 of 22 min. At the highest dose, the maternal systemic vascular resistance dropped 49% in association with a 59% increase in heart rate. The uterine blood flow decreased 29%. Tachycardia was the only significant effect in the fetus. In a subgroup of sheep, chronic dosing with phenobarbital increased maternal nifedipine clearance 3-fold.
Department of Obstetrics and Gynecology, George Washington University Medical Center.
C E
CE
Nugent
M
M
Hill
T
T
Hursey
F P
FP
Abramson
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D009543:Nifedipine / Q000493:pharmacokinetics / Q000494:pharmacology*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism* / Q000502:physiology; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects
D009543:Nifedipine