The pharmacokinetics of glyceryl trinitrate with the use of the in vitro term human placental perfusion setup

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

“…The steady-state UV [GTN] was 17 nM, and the UV/MA GTN concentration ratio was 0.18. The steady-state fetal/maternal GTN concentration ratio using the in vitro perfused human placenta (UV/MA = 0.20) (Bustard et al 2002) was similar to the ratio in the present study, and suggests that GTN crosses the human (hemomonochorial) and ovine (syndesmo-chorial) placentas with approximately the same kinetic profile.…”

“…Although species differences also likely contribute to differences in drug kinetics, the results from the present study in sheep enable the generation of time-course kinetic information unattainable in human studies. Because the steady-state GTN concentration ratio for preterm sheep in vivo (UV/MA = 0.18) was the same as the human placental in vitro ratio (UV/MA = 0.20) (Bustard et al 2002), the sheep preparation is an appropriate model for assessing in vivo steady-state GTN levels across the placenta. We have also reported that during transdermal GTN administration (0.4 mg/h) the steady-state FV (UV equivalent)/MV concentration ratio was less than 0.25 at the time of investigative fetal blood sampling in preterm women (Bustard et al 2002b).…”

“…The extraction and chromatographic analysis of the plasma samples has been previously described (Booth et al 1990). Briefly, plasma samples were assayed for drug and metabolite content using gas-liquid chromatography (Hewlett-Packard (HP) 6890 gas chromatograph with 63 Ni electron-capture detector, and HP Chem-Station software, Hewlett-Packard Company, Palo Alto, Calif.) (Bustard et al 2002). All plastics used were polyethylene or polypropylene, and the glassware was silanized to prevent adsorption of analytes (Booth et al 1991).…”

“…The administration of vasoactive drugs in pregnancy requires caution because of potential uteroplacental and cardiovascular alterations, and thus the disposition of GTN in pregnancy must be determined. In the term in vitro human placental perfusion preparation, we recently demonstrated that during continuous maternal arterial (MA) GTN perfusion (100 nM) the fetal venous (FV, umbilical venous equivalent) to MA ratio (FV/MA) of GTN was approximately 0.2 (Bustard et al 2002). No work has investigated the cross-placental transfer of GTN during steady-state administration in utero.…”

The Effect of Glyceryl Trinitrate on Hypertension in Women with Severe Preeclampsia, HELLP Syndrome, and Eclampsia

“…No change in fetal heart rate has been reported with use of GTN in pregnancy which would be expected if hypotension occurred (10). In a recent study investigating the in vitro crossplacental transfer of GTN, Bustard et al (12) demonstrated that GTN, at a tocolytic concentration, can cross the placenta with a fetal:maternal ratio of 18.5, but was not found to affect fetal arterial perfusion pressure. In animal experiments no significant changes have been reported in cardiovascular parameters or in the acidbase status in the fetus either during or after glycerol trinitrate infusion.…”