Human maternal and fetal plasma glyceryl trinitrate concentrations.
OBJECTIVE
This study was undertaken to determine the maternal and fetal steady-state concentrations of glyceryl trinitrate (GTN) and its dinitrate metabolites during transdermal administration, at the time of fetal blood sampling for obstetric indications.


METHODS
Transdermal GTN (0.4 mg/h) was applied approximately 2 hours before investigative fetal blood sampling to maintain uterine quiescence. Serial maternal venous (MV) and a single fetal venous (FV) plasma samples were collected and assayed for GTN and its metabolites, 1,2- and 1,3-glyceryl dinitrate.


RESULTS
The steady-state MV plasma concentration was 4.3+/-0.84 nmol/L (mean+/-SEM, n=7), and the dinitrate metabolites were detectable in the MV but not quantifiable. GTN was detectable in the FV (n=7) but was not quantifiable as the levels were less than the lower limit of sensitivity of the assay (<1 nmol/L).


CONCLUSIONS
During transdermal GTN administration, the steady-state FV/MV concentration ratio is less than 0.23 at the time of fetal blood sampling.
Bustard
Mark A
MA
Department of Pharmacology and Toxicology, Queen's University, Kingston General Hospital, 76 Stuart Street, Kingston, Ontario, Canada K7L 2V7.
Ryan
Greg
G
Seaward
Gareth
G
Saleniak
Mary-Ellen
ME
Smith
Graeme N
GN
D000279:Administration, Cutaneous; D001682:Biological Availability; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D005865:Gestational Age; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D005996:Nitroglycerin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007752:Obstetric Labor, Premature / Q000517:prevention & control; D011247:Pregnancy / Q000097:blood*; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D015149:Tocolytic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*
D015149:Tocolytic Agents; D005996:Nitroglycerin