RT Journal Article
SR Electronic
T1 Pharmacokinetics and pharmacodynamics of nifedipine in pregnant sheep.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 754
OP 757
VO 19
IS 4
A1 C E Nugent
A1 M Hill
A1 T Hursey
A1 F P Abramson
YR 1991
UL http://dmd.aspetjournals.org/content/19/4/754.abstract
AB 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.