Insignificant transfer of glyburide occurs across the human placenta

doi:10.1016/0002-9378(91)90421-M

American Journal of Obstetrics and Gynecology

Volume 165, Issue 4, Part 1, October 1991, Pages 807-812

https://doi.org/10.1016/0002-9378(91)90421-M Get rights and content

Abstract

No data exist concerning human placental transfer of oral hypoglycemic agents during pregnancy. This study characterizes the transport of glyburide in 10 term human placentas with the single-cotyledon placental model. Serial samples were taken from both the maternal and fetal reservoirs during each 3-hour perfusion, and the percent transport and metabolism of tritiated glyburide was calculated with liquid scintillation spectrometry and high-performance liquid chromatography. Antipyrine labeled with carbon 14 was added to the perfusate solution during these experiments as a control. Virtually no transfer of glyburide occurred, and no appreciable metabolism of the drug was detected. Neither variation in the albumin concentration nor increase in the maternal glyburide levels to 100 times therapeutic concentration materially altered the rate of transport. These data show that insignificant transport of glyburide occurs across the human placenta in vitro and suggest that fetal exposure to maternally administered glyburide likewise may be insignificant.

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Citation Excerpt :
We will consider especially the oral anti-diabetic medications – metformin and glyburide, compared to either a dietary regimen or insulin. Importantly, as metformin is known to cross the placenta to a greater extent than glyburide [14], and cord blood concentrations are higher than maternal ones, it can to provide larger direct fetal effects and not just via maternal glycemic control. Possibly, and yet to be proven, in utero exposure to metformin, for infants of diabetic mothers, may lead to programming effects such as improved insulin sensitivity, with beneficial effects on birthweight, body mass index and the mass and distribution of adipose tissue.
Diabetes is a frequent condition in pregnancy and achieving adequate glycemic control is of paramount importance. Insulin treatment is the gold standard, oral agents are more attractive, but their safety and efficiency should be a prerequisite for their use.
We have more information regarding treatment of women with gestational diabetes mellitus where glyburide can induce a picture of fetal hyperinsulinism (higher birthweight and more neonatal hypoglycemia) whereas metformin requires supplemental insulin in a larger proportion of women but achieves satisfactory perinatal outcomes with the exception of preterm birth. Information in patients with Type 2 Diabetes Mellitus is much more limited but also favors metformin. Combinations provide additional possibilities.
However, as to long-term outcomes, we have no information on the impact of exposure to glyburide and it is still unclear if in utero exposure to metformin will have any effect on the offspring and the direction of this effect.
Women prefer oral agents, indicating the need of additional studies.

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: Presented at the Eleventh Annual Meeting of the Society of Perinatal Obstetricians, San Francisco, California, January 28 -February 2, 1991.

^*: From the Department of Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio.

View full text

Insignificant transfer of glyburide occurs across the human placenta

Abstract

Am J Obstet Gynecol

J Pediatr

Am J Obstet Gynecol

J Chromatogr

J Chromatogr

Alcohol

Management of diabetes mellitus and pregnancy: a survey of obstetricians and maternal- fetal specialists

Obstet Gynecol

Transplacental passage of insulin in pregnant women with insulindependent diabetes mellitus

N Engl J Med