Effects of rifampin on the pharmacokinetics and pharmacodynamics of glyburide and glipizide

Clin Pharmacol Ther. 2001 Jun;69(6):400-6. doi: 10.1067/mcp.2001.115822.


Objective: To study the effects of rifampin (INN, rifampicin) on the pharmacokinetics and pharmacodynamics of glyburide (INN, glibenclamide) and glipizide, 2 sulfonylurea antidiabetic drugs.

Methods: Two separate, randomized, 2-phase, crossover studies with an identical design were conducted. In each study, 10 healthy volunteers received 600 mg rifampin or placebo once daily for 5 days. On day 6, a single dose of 1.75 mg glyburide (study I) or 2.5 mg glipizide (study II) was administered orally. Plasma glyburide and glipizide and blood glucose concentrations were measured for 12 hours.

Results: In study I, rifampin decreased the area under the plasma concentration--time curve [AUC(0-infinity)] of glyburide by 39% (P <.001) and the peak plasma concentration by 22% (P =.01). The elimination half-life of glyburide was shortened from 2.0 to 1.7 hours (P <.05) by rifampin. The blood glucose decremental AUC(0-7) (net area below baseline) and the maximum decrease in the blood glucose concentration were decreased by 44% (P =.05) and 36% (P <.001), respectively, by rifampin. In study II, rifampin decreased the AUC(0-infinity) of glipizide by 22% (P <.05) and shortened its half-life from 3.0 to 1.9 hours (P =.01). No statistically significant differences in the blood glucose concentrations were found between the phases; however, 4 subjects had moderate hypoglycemia during the placebo phase but only 1 subject had moderate hypoglycemia during the rifampin phase.

Conclusions: Rifampin moderately decreased the plasma concentrations and effects of glyburide but had only a slight effect on glipizide. The mechanism underlying the interaction between rifampin and glyburide is probably induction of either CYP2C9 or P-glycoprotein or both. Induction of CYP2C9 would explain the increased systemic elimination of glipizide. It is probable that the blood glucose--lowering effect of glyburide is reduced during concomitant treatment with rifampin. In some patients, the effects of glipizide may also be reduced by rifampin.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibiotics, Antitubercular / pharmacology*
  • Area Under Curve
  • Blood Glucose / metabolism
  • Female
  • Glipizide / blood
  • Glipizide / pharmacokinetics*
  • Glyburide / blood
  • Glyburide / pharmacokinetics*
  • Half-Life
  • Humans
  • Hypoglycemic Agents / blood
  • Hypoglycemic Agents / pharmacokinetics*
  • Male
  • Rifampin / pharmacology*


  • Antibiotics, Antitubercular
  • Blood Glucose
  • Hypoglycemic Agents
  • Glyburide
  • Rifampin
  • Glipizide