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, beta-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 approximately 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 beta-cell responsivity indices, the average beta-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.
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Authors | M F Hebert, X Ma, S B Naraharisetti, K M Krudys, J G Umans, G D V Hankins, S N Caritis, M Miodovnik, D R Mattison, J D Unadkat, E J Kelly, D Blough, C Cobelli, M S Ahmed, W R Snodgrass, D B Carr, T R Easterling, P Vicini, Obstetric-Fetal Pharmacology Research Unit Network |
Journal | Clinical pharmacology and therapeutics
(Clin Pharmacol Ther)
Vol. 85
Issue 6
Pg. 607-14
(Jun 2009)
ISSN: 1532-6535 [Electronic] United States |
PMID | 19295505
(Publication Type: Clinical Trial, Comparative Study, Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Blood Glucose
- Hypoglycemic Agents
- CYP2C9 protein, human
- Cytochrome P-450 CYP2C9
- Aryl Hydrocarbon Hydroxylases
- Glyburide
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Topics |
- Adult
- Area Under Curve
- Aryl Hydrocarbon Hydroxylases
- Blood Glucose
(analysis)
- Cytochrome P-450 CYP2C9
- Diabetes Mellitus, Type 2
(drug therapy)
- Diabetes, Gestational
(drug therapy)
- Dose-Response Relationship, Drug
- Female
- Fetal Blood
(chemistry)
- Glyburide
(pharmacokinetics, therapeutic use)
- Humans
- Hypoglycemic Agents
(pharmacokinetics, therapeutic use)
- Insulin Resistance
- Insulin-Secreting Cells
(drug effects, physiology)
- Metabolic Clearance Rate
- Monte Carlo Method
- Pregnancy
- Pregnancy Trimester, Third
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