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Are We Optimizing Gestational Diabetes Treatment With Glyburide? The Pharmacologic Basis for Better Clinical Practice
Author(s) -
Hebert MF,
Ma X,
Naraharisetti SB,
Krudys KM,
Umans JG,
Hankins GDV,
Caritis SN,
Miodovnik M,
Mattison DR,
Unadkat JD,
Kelly EJ,
Blough D,
Cobelli C,
Ahmed MS,
Snodgrass WR,
Carr DB,
Easterling TR,
Vicini P
Publication year - 2009
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2009.5
Subject(s) - medicine , obstetrics and gynaecology , library science , family medicine , pregnancy , genetics , biology , computer science
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. Clinical Pharmacology & Therapeutics (2009); 85 , 6, 607–614 doi: 10.1038/clpt.2009.5