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Glyburide crosses the placenta in vivo in pregnant rats
Open accessAbstract
Non-insulin-dependent diabetes mellitus (NIDDM) is normally treated by oral hypoglycaemic agents, but their use is excluded during pregnancy because of their potential teratogenic and hypoglycaemic effects on the fetus. This caveat was recently questioned as glyburide was shown to cross an isolated cotyledon in vitro in insignificant amounts. In the present study, placental transport of glyburide in vivo was examined as an indispensable step towards clinical trials. Tritiated glyburide, C14 albumin or C14-labelled diazepam were injected into 13, 9 and 11 pregnant rats, respectively and the radioactivity was measured thereafter in maternal blood and in whole fetal extracts. The ratios between radioactivity in fetal tissue to that in maternal blood for glyburide (0.535 +/- 0.068) were similar to those of diazepam (0.641 +/- 0.057) which readily crosses the placenta. However, they differed significantly from those for albumin (0.048 +/- 0.0004) which does not cross. Moreover, glyburide in fetal tissue consistently reflected its concentration in maternal blood when measured at consecutive intervals after intravenous injection in the mother. In contrast, albumin in fetal tissue was low at all time points regardless of its levels in maternal blood when measured at different times after injection. These data suggest that glyburide crosses the placenta of pregnant rats and should therefore be considered with caution as a hypoglycaemic agent in the treatment of gestational diabetes.
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It is unlikely that the albumin fusion protein albiglutide crosses the placenta because albumin does not cross the hemochorial placenta.
“Since albumin does not cross the hemochorial placenta, as shown in the rat (60), guinea pig (61) and in vitro in a human placenta (62), it seems unlikely that the albumin fusion protein albiglutide should cross the placenta.”
From Effects of GLP-1 agonists and SGLT2 inhibitors during pregnancy and lactation on offspring outcomes: a systematic review of the evidence (2023) · cites this paper as [60]
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References 16 · Cited by 44
Research works printed but not linked: 1
- Coetzee EJ, Jackson WPU (1980) Pregnancy in established non-insulin-dependent diabetics. S Afr Med J 58: 795–802
Metadata
- Authors
- Sivan, E., Feldman, B., Dolitzki, M., Nevo, N., Dekel, N., & Karasik, A.
- Affiliations
- Sheba Medical Center (IL)
- Weizmann Institute of Science (IL)
- ORCID
- Venue
- Diabetologia
- Published
- 1995-07
- Volume
- 38
- Issue
- 7
- Pages
- 753-756
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2115330378
- Cited by
- 44
- References
- 16
- Citations by year
- 2024: 1 · 2023: 1 · 2021: 1 · 2019: 1 · 2018: 2 · 2017: 1 · 2015: 2 · 2014: 3 · 2013: 2 · 2012: 1
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Keywords
- glibenclamide, placental transfer, gestational diabetes mellitus, type 2 diabetes, oral antidiabetic drugs, drug safety in pregnancy, prenatal drug exposure, albumin, diazepam, pregnant rats
- MeSH terms
- Animals, Carbon Radioisotopes, Diazepam, Female, Fetus, Gestational Age, Glyburide, Hypoglycemic Agents, Maternal-Fetal Exchange, Pregnancy, Serum Albumin, Teratogens, Time Factors, Rats, Wistar, Rats
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