PT  - JOURNAL ARTICLE
AU  - C E Nugent
AU  - M Hill
AU  - T Hursey
AU  - F P Abramson
TI  - Pharmacokinetics and pharmacodynamics of nifedipine in pregnant sheep.
DP  - 1991 Jul 01
TA  - Drug Metabolism and Disposition
PG  - 754--757
VI  - 19
IP  - 4
4099  - http://dmd.aspetjournals.org/content/19/4/754.short
4100  - http://dmd.aspetjournals.org/content/19/4/754.full
SO  - Drug Metab Dispos1991 Jul 01; 19
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.