Steady-state maternal and fetal plasma concentrations of glyceryl trinitrate (GTN) in the preterm sheep

Abstract

The administration of glyceryl trinitrate (GTN; nitroglycerin) is increasing during preterm pregnancies, yet its disposition and, importantly, the extent of fetal exposure remain to be elucidated. When used as a tocolytic (pharmacological agent that stops uterine contractions), it is administered transdermally (24–48 h). Here, we quantified the maternal and fetal steady-state plasma concentrations of maternal intravenous GTN in preterm sheep and continuously monitored maternal and fetal vascular parameters to observe possible dose-dependant vascular effects. Preterm (120 days gestation) pregnant sheep (n = 6) were instrumented with maternal femoral arterial (MA) and venous (MV) and fetal femoral arterial (FA) and umbilical venous (UV) polyethylene blood-sampling catheters. During maternal GTN infusion (3.0 µg·kg–1·min–1, 60-min duration) the steady-state GTN concentrations ([GTN]) were as follows: MA, 98.6 ± 9.0 nM; UV, 17.4 ± 7.6 nM; and FA, <5 nM. There were no changes in maternal and fetal mean arterial pressure and heart rate or in uterine activity. Overall, the steady-state [GTN] was established by 5 min, and the UV/MA ratio of [GTN] was 0.18. The FA [GTN] (<5 nM) indicates that the fetus cleared essentially all GTN in the UV, and the maternal and fetal heart rate and mean arterial pressure appear to be independent of maternal GTN infusion.Key words: nitroglycerin, pharmacokinetics, maternal-fetal exchange, pregnancy, cardiovascular.