Nugent C E, Hill M, Hursey T, Abramson F P
Department of Obstetrics and Gynecology, George Washington University Medical Center.
Drug Metab Dispos. 1991 Jul-Aug;19(4):754-7.
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.
通过四级静脉输注，以1 - 10微克/千克/分钟的速率向怀孕绵羊施用钙通道阻滞剂硝苯地平。测量母体和胎儿血浆硝苯地平浓度以及母体和胎儿的心率、血压、pH值和血气。两室母体药代动力学显示快速相半衰期为11分钟，慢速相半衰期为137分钟。药物通过一级过程到达胎儿，半衰期为22分钟。在最高剂量下，母体全身血管阻力下降49%，同时心率增加59%。子宫血流量减少29%。心动过速是对胎儿唯一的显著影响。在一组绵羊亚组中，苯巴比妥的长期给药使母体硝苯地平清除率增加了3倍。
