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

Objective: To study the effects of rifampin (INN, rifampicin) on the pharma cokinetics and pharmacodynamics of glyburide (INN, glibenclamide) and glipi zide, 2 sulfonylurea antidiabetic drugs. Methods: Two separate, randomized, 2-phase, crossover studies with an ident ical design were conducted. In each study, 10 healthy volunteers received 6 00 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 administere d orally. Plasma glyburide and glipizide and blood glucose concentrations w ere measured for 12 hours. Results: In study I, rifampin decreased the area under the plasma concentra tion-time curve [AUC(0-infinity)] of glyburide by 39% (P < .001) and the pe ak plasma concentration by 22% (P = .01). The elimination half-life of glyb uride 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 decr ease 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-l ife from 3.0 to 1.9 hours (P = .01). No statistically significant differenc es in the blood glucose concentrations were found between the phases; howev er, 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 ef fects of glyburide but had only a slight effect on glipizide. The mechanism underlying the interaction between rifampin and glyburide is probably indu ction of either CYP2C9 or P-glycoprotein or both. Induction of CYP2C9 would explain the increased systemic elimination of glipizide. It is probable th at the blood glucose-lowering effect of glyburide is reduced during concomi tant treatment with rifampin. In some patients, the effects of glipizide ma y also be reduced by rifampin.