Are We Optimizing Gestational Diabetes Treatment With Glyburide? The Pharmacologic Basis for Better Clinical Practice
2009; Wiley; Volume: 85; Issue: 6 Linguagem: Inglês
10.1038/clpt.2009.5
ISSN1532-6535
AutoresMary F. Hébert, Xuetao Ma, SB Naraharisetti, K M Krudys, JG Umans, G.D.V. Hankins, Steve N. Caritis, Menachem Miodovnik, Donald R. Mattison, Jashvant D. Unadkat, EJ Kelly, David K. Blough, Claudio Cobelli, Mahmoud Ahmed, W R Snodgrass, DB Carr, TR Easterling, P. Vicini,
Tópico(s)Pregnancy and preeclampsia studies
ResumoGlyburide'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. Clinical Pharmacology & Therapeutics (2009); 85, 6, 607–614 doi:10.1038/clpt.2009.5
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