Glyburide transport across the human placenta.
OBJECTIVE
To estimate the magnitude of transplacental transfer of glyburide in women with gestational diabetes mellitus (GDM).


METHODS
A prospective, observational study was conducted on women with GDM on glyburide therapy. On delivery admission, the glyburide dose and time of last dose were recorded. Immediately postdelivery, maternal and umbilical venous blood samples were obtained and the concentrations of glyburide were determined by high-performance liquid chromatography-mass spectrometry with a limit of detection of 0.25 ng/mL.


RESULTS
Nineteen patient dyads were analyzed. The mean total daily maternal glyburide dose was 6.6±6.3 mg per day and the mean time between last dose and sampling was 13.3±6.5 hours. The mean maternal serum glyburide level at birth was 15.4±20.8 ng/mL, whereas the mean umbilical glyburide level was 7.5±8.2 ng/mL, which showed a statistical correlation (r=0.72, P<.01). There were statistically significant relationships between total maternal glyburide dose (1.25-20 mg per day) and maternal glyburide levels (0.93-70.71 ng/mL; r=0.46, P≤.01) and between total maternal glyburide dose and umbilical glyburide levels (0.95-32.41 ng/mL; r=0.43, P≤.01) However, we observed wide variability in maternal and umbilical glyburide levels at both extremes of the total glyburide dose. Seventy-nine percent of cord samples (15/19) had glyburide levels less than 10 ng/mL (the limit of detection reported in earlier studies) and 37% (7/19) were higher than the corresponding maternal samples.


CONCLUSIONS
Transplacental transfer of glyburide is highly variable among patients, corroborating ex vivo placental perfusion studies showing a transport-mediated glyburide efflux from the fetal to the maternal circulation. In most neonates (79%), glyburide levels were below 10 ng/mL.


METHODS
III.
Department of Obstetrics and Gynecology, St. Luke's-Roosevelt Hospital Center, New York, New York; and the Division of Clinical Pharmacology/Toxicology, The Hospital for Sick Children, and the Leslie Dan School of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
Rachelle A
RA
Schwartz
Barak
B
Rosenn
Katarina
K
Aleksa
Gideon
G
Koren
D000328:Adult; D016640:Diabetes, Gestational / Q000188:drug therapy*; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005905:Glyburide / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011446:Prospective Studies
D007004:Hypoglycemic Agents; D005905:Glyburide