Are we optimizing gestational diabetes treatment with glyburide? The pharmacologic basis for better clinical practice.
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.
Hebert
M F
MF
Department of Pharmacy, University of Washington, Seattle, Washington, USA. mhebert@u.washington.edu
Ma
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Naraharisetti
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Krudys
K M
KM
Umans
J G
JG
Hankins
G D V
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Caritis
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Miodovnik
M
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Mattison
D R
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Unadkat
J D
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Kelly
E J
EJ
Blough
D
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Cobelli
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Ahmed
M S
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Snodgrass
W R
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Carr
D B
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Easterling
T R
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Vicini
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D000328:Adult; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases; D001786:Blood Glucose / Q000032:analysis; D065729:Cytochrome P-450 CYP2C9; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D016640:Diabetes, Gestational / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005905:Glyburide / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology; D008657:Metabolic Clearance Rate; D009010:Monte Carlo Method; D011247:Pregnancy; D011263:Pregnancy Trimester, Third
D001786:Blood Glucose; D007004:Hypoglycemic Agents; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D005905:Glyburide