title: Are we optimizing gestational diabetes treatment with glyburide? The pharmacologic basis for better clinical practice.
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.
authors.affiliation: Department of Pharmacy, University of Washington, Seattle, Washington, USA. mhebert@u.washington.edu
authors.forename: M F
authors.initials: MF
authors.lastname: Hebert
authors.forename: X
authors.initials: X
authors.lastname: Ma
authors.forename: S B
authors.initials: SB
authors.lastname: Naraharisetti
authors.forename: K M
authors.initials: KM
authors.lastname: Krudys
authors.forename: J G
authors.initials: JG
authors.lastname: Umans
authors.forename: G D V
authors.initials: GD
authors.lastname: Hankins
authors.forename: S N
authors.initials: SN
authors.lastname: Caritis
authors.forename: M
authors.initials: M
authors.lastname: Miodovnik
authors.forename: D R
authors.initials: DR
authors.lastname: Mattison
authors.forename: J D
authors.initials: JD
authors.lastname: Unadkat
authors.forename: E J
authors.initials: EJ
authors.lastname: Kelly
authors.forename: D
authors.initials: D
authors.lastname: Blough
authors.forename: C
authors.initials: C
authors.lastname: Cobelli
authors.forename: M S
authors.initials: MS
authors.lastname: Ahmed
authors.forename: W R
authors.initials: WR
authors.lastname: Snodgrass
authors.forename: D B
authors.initials: DB
authors.lastname: Carr
authors.forename: T R
authors.initials: TR
authors.lastname: Easterling
authors.forename: P
authors.initials: P
authors.lastname: Vicini
mesh_terms: 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
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D005905:Glyburide