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

OBJECTIVE: The purpose of this study was to determine the pharmacokinetics of glyceryl trintrate across the in vitro term human perfused placenta. STUDY DESIGN: Peripheral placental lobules (n = 6) were dually perfused. The maternal side was perfused with glyceryl trinitrate (100 nmol/L) for 90 minutes. Serial samples from the fetal venous and maternal venous catheters were collected and assayed for glyceryl trinitrate and its vasoactive metabolites (1,2- and 1,3-glyceryl dinitrate) with gas chromatography. Fetal arterial perfusion pressure was continuously measured throughout. Data are expressed as the mean +/- SEM, with 1-way analysis of variance followed by a Newman-Keuls post-hoc test (P < .05). RESULTS: The mean steady-state fetal venous:maternal side ratio of glyceryl trinitrate concentration was 18.5% +/- 3.7%. The 1,2-glyceryl dinitrate and 1,3-glyceryl dinitrate levels in the fetal venous samples and maternal venous samples were less than the lower end of the sensitivity range of the assay (<5 nmol/L). Fetal arterial perfusion pressure did not change with glyceryl trintrate administration. CONCLUSION: The glyceryl trinitrate in the fetal venous sample was approximately 18.5% of the glyceryl trinitrate in the maternal side in this preparation. The presence of glyceryl dinitrates in the maternal venous samples and the fetal venous samples indicates the capacity for placental biotransformation of glyceryl trinitrate. The data demonstrate that glyceryl trinitrate, at a tocolytic concentration, has the ability to cross the placenta but was not found to affect fetal arterial perfusion pressure.