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,
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2022, Reproductive and Developmental ToxicologyGlibenclamide transfer across the perfused human placenta is determined by albumin binding not transporter activity
2020, European Journal of Pharmaceutical SciencesCitation Excerpt :It is thought that only the free fraction of glibenclamide can be transported across a cell membrane and it has been reported that under physiological conditions, the free fraction of glibenclamide is only 0.2% (Koren, 2001; Nanovskaya et al., 2006). Ex vivo human placental perfusion studies have demonstrated significantly higher glibenclamide transfer in the fetal to maternal direction compared to the maternal to fetal direction, consistent with the activity of efflux pumps on the MVM (Kraemer et al., 2006). This was attributed to BCRP, as opposed to P-gp or MRPs, based on studies using the BCRP inhibitor nicardipine and the lack of effect of the P-gp inhibitor verapamil and the MRP inhibitor indomethacin, combined with the low expression of MRPs (Gedeon et al., 2008; Kraemer et al., 2006; Pollex et al., 2008).
Management of gestational diabetes mellitus to optimize outcomes
2020, Obesity and ObstetricsEndocrine Diseases of Pregnancy
2019, Yen & Jaffe's Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management: Eighth EditionPharmacological treatment of gestational diabetes mellitus: point/counterpoint
2018, American Journal of Obstetrics and Gynecology
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.