Are we optimizing gestational diabetes treatment with glyburide the pharmacologic basis for better clinical practice

M. F. Hebert, X. Ma, S. B. Naraharisetti, K. M. Krudys, J. G. Umans, Gary Hankins, S. N. Caritis, M. Miodovnik, D. R. Mattison, J. D. Unadkat, E. J. Kelly, D. Blough, C. Cobelli, Mahmoud Ahmed, W. R. Snodgrass, D. B. Carr, T. R. Easterling, P. Vicini

Research output: Contribution to journalArticle

138 Citations (Scopus)

Abstract

Glyburide's pharmacokinetics (PK) and pharmacodynamics have not been studied in women with gestational diabetes mellitus (GDM). The objective of this study was to assess steady-state PK of glyburide, as well as insulin sensitivity, Β-cell responsivity, and overall disposition indices after a mixed-meal tolerance test (MMTT) in women with GDM (n = 40), nonpregnant women with type 2 diabetes mellitus (T2DM) (n = 26), and healthy pregnant women (n = 40, MMTT only). At equivalent doses, glyburide plasma concentrations were ∼50% lower in pregnant women than in nonpregnant subjects. The average umbilical cord/maternal plasma glyburide concentration ratio at the time of delivery was 0.7 0.4. Insulin sensitivity was approximately fivefold lower in women with GDM as compared with healthy pregnant women. Despite comparable Β-cell responsivity indices, the average Β-cell function corrected for insulin resistance was more than 3.5-fold lower in women with glyburide-treated GDM than in healthy pregnant women. Women with GDM in whom glyburide treatment has failed may benefit from alternative medication or dosage escalation; however, fetal safety should be kept in mind.

Original languageEnglish (US)
Pages (from-to)607-614
Number of pages8
JournalClinical Pharmacology and Therapeutics
Volume85
Issue number6
DOIs
StatePublished - Jun 2009

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Gestational Diabetes
Glyburide
Pregnant Women
Insulin Resistance
Meals
Therapeutics
Pharmacokinetics
Umbilical Cord
Type 2 Diabetes Mellitus
Mothers
Safety

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Hebert, M. F., Ma, X., Naraharisetti, S. B., Krudys, K. M., Umans, J. G., Hankins, G., ... Vicini, P. (2009). Are we optimizing gestational diabetes treatment with glyburide the pharmacologic basis for better clinical practice. Clinical Pharmacology and Therapeutics, 85(6), 607-614. https://doi.org/10.1038/clpt.2009.5

Are we optimizing gestational diabetes treatment with glyburide the pharmacologic basis for better clinical practice. / Hebert, M. F.; Ma, X.; Naraharisetti, S. B.; Krudys, K. M.; Umans, J. G.; Hankins, Gary; Caritis, S. N.; Miodovnik, M.; Mattison, D. R.; Unadkat, J. D.; Kelly, E. J.; Blough, D.; Cobelli, C.; Ahmed, Mahmoud; Snodgrass, W. R.; Carr, D. B.; Easterling, T. R.; Vicini, P.

In: Clinical Pharmacology and Therapeutics, Vol. 85, No. 6, 06.2009, p. 607-614.

Research output: Contribution to journalArticle

Hebert, MF, Ma, X, Naraharisetti, SB, Krudys, KM, Umans, JG, Hankins, G, Caritis, SN, Miodovnik, M, Mattison, DR, Unadkat, JD, Kelly, EJ, Blough, D, Cobelli, C, Ahmed, M, Snodgrass, WR, Carr, DB, Easterling, TR & Vicini, P 2009, 'Are we optimizing gestational diabetes treatment with glyburide the pharmacologic basis for better clinical practice', Clinical Pharmacology and Therapeutics, vol. 85, no. 6, pp. 607-614. https://doi.org/10.1038/clpt.2009.5
Hebert, M. F. ; Ma, X. ; Naraharisetti, S. B. ; Krudys, K. M. ; Umans, J. G. ; Hankins, Gary ; Caritis, S. N. ; Miodovnik, M. ; Mattison, D. R. ; Unadkat, J. D. ; Kelly, E. J. ; Blough, D. ; Cobelli, C. ; Ahmed, Mahmoud ; Snodgrass, W. R. ; Carr, D. B. ; Easterling, T. R. ; Vicini, P. / Are we optimizing gestational diabetes treatment with glyburide the pharmacologic basis for better clinical practice. In: Clinical Pharmacology and Therapeutics. 2009 ; Vol. 85, No. 6. pp. 607-614.
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