General Obstetrics and Gynecology: ObstetricsPerfusion studies of glyburide transfer across the human placenta: Implications for fetal safety
Section snippets
In vitro perfusion of placental cotyledon
Placentas were obtained immediately after delivery from elective cesarean sections and were transported to the laboratory in ice-cold heparinized phosphate-buffered saline. Maternal and fetal circulations were established to a peripheral lobule as previously described by our laboratory.11 Perfusion of the placental cotyledon was established within 30 minutes of delivery of the infant.
The perfusate (maintained at 37°C) consisted of a tissue culture medium (M199, Sigma, St. Louis, MO) that
Results
The physical and viability parameters of all perfusion experiments conducted are presented in Table I. The mean (± SD) mass of the perfused cotyledons was 16.6 ± 2 (range 9.8 to 25.7). There was no significant difference in the fetal arterial pressures between the experimental and the control periods (mean ± SD) (Table I). The production of lactate and hCG as well as the rate of consumption of glucose and oxygen did not vary between the experimental and the control periods. There was no
Comment
This study provides the first evidence of transplacental efflux against a concentration gradient of glyburide from the fetal to the maternal circulation in humans. It is also the first evidence of active efflux of any medicinal drug used in human pregnancy.
In 1994 Elliott et al,14 using a similar model, showed that significantly less glyburide introduced in the maternal circulation finds itself into the fetal circulation, as compared with other oral hypoglycemics (eg, chlorpropamide,
References (16)
- et al.
Glyburide for the treatment of gestational diabetes
Am J Obstet Gynecol
(2004) A validated method for the determination of verapamil and norverapamil in human plasma
J Pharm Biomed Anal
(2001)- et al.
Comparative placental transport of oral hypoglycemic agents in humans: a model of human placental drug transfer
Am J Obstet Gynecol
(1994) Drugs in pregnancy and lactation
(2005)Maternal-Fetal Toxicology
(2001)- et al.
Maternal-fetal transport of hypoglycaemic drugs
Clin Pharmacokinet
(2003) - et al.
A comparison of glyburide and insulin in women with gestational diabetes mellitus
N Engl J Med
(2000) - et al.
Prospective observational study to establish predictors of glyburide success in women with gestational diabetes mellitus
J Perinatol
(2004)
Cited by (0)
Supported by a grant from the Canadian Institute for Health Research. G.K. is holder of the Ivey Chair in Molecular Toxicology at the University of Western Ontario and the Research Leadership in Better Pharmacotherapy During Pregnancy and Lactation at the Hospital for Sick Children.