title: Effects of aspirin and ibuprofen on the pharmacokinetics and pharmacodynamics of glyburide in healthy subjects.
abstract: OBJECTIVE
  To determine the effects of aspirin and ibuprofen on the pharmacokinetics and pharmacodynamics of glyburide in healthy volunteers.
  
  
  METHODS
  Single-center, randomized, two-way, crossover design following an initial baseline evaluation phase.
  
  
  METHODS
  Outpatient, university-based ambulatory care facility.
  
  
  METHODS
  Sixteen healthy nonsmoking men aged 20-34 years.
  
  
  METHODS
  Three phases consisting of six treatments. Phase 1 began with treatment A, a baseline oral glucose tolerance test (GTT), followed by treatment B, glyburide 5 mg plus a GTT. The other two phases were administered in a crossover design. Phase 2 consisted of the administration of aspirin 975 mg qid for 4 days. On day 3 a GTT was administered (treatment C) and on day 4 glyburide 5 mg plus a GTT was administered (treatment E). Phase 3 consisted of the administration of ibuprofen 600 mg qid for 4 days with a GTT on day 3 (treatment D) and glyburide 5 mg plus a GTT on day 4 (treatment F).
  
  
  METHODS
  Serum glyburide concentrations after each treatment, as well as glucose and insulin, ibuprofen, and salicylate serum concentrations and glyburide free fractions.
  
  
  RESULTS
  Aspirin administration resulted in an 85% increase in mean total glyburide oral clearance and a 29% increase in glyburide free fraction. Ibuprofen administration resulted in a slight increase in mean glyburide free fraction, but no significant changes in glyburide pharmacokinetic parameters were observed. Insulin concentrations were increased during the glyburide plus aspirin treatment. Conflicting results were observed in the glucose parameters.
  
  
  CONCLUSIONS
  The potential for this glyburide-aspirin interaction resulting in a transient hypoglycemia should be considered in diabetic patients receiving glyburide therapy.
authors.affiliation: Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, PA 15261, USA.
authors.forename: R T
authors.initials: RT
authors.lastname: Kubacka
authors.forename: E J
authors.initials: EJ
authors.lastname: Antal
authors.forename: R P
authors.initials: RP
authors.lastname: Juhl
authors.forename: I R
authors.initials: IR
authors.lastname: Welshman
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D004347:Drug Interactions; D005951:Glucose Tolerance Test; D005905:Glyburide / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000493:pharmacokinetics*; D007052:Ibuprofen / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008297:Male
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D001241:Aspirin; D005905:Glyburide; D007052:Ibuprofen