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Effect of rifampicin on the pharmacokinetics and pharmacodynamics of glimepiride.

Author(s): Niemi M, Kivisto KT, Backman JT, Neuvonen PJ

Affiliation(s): Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.

Publication date & source: 2000-12, Br J Clin Pharmacol., 50(6):591-5.

Publication type: Clinical Trial; Randomized Controlled Trial

AIMS: To study the effects of rifampicin on the pharmacokinetics and pharmaco-dynamics of glimepiride, a new sulphonylurea antidiabetic drug. METHODS: In this randomised, two-phase cross-over study, 10 healthy volunteers were treated for 5 days with 600 mg rifampicin or placebo once daily. On day 6, a single oral dose of 1 mg glimepiride was administered. Plasma glimepiride and blood glucose concentrations were measured up to 12 h. RESULTS: Rifampicin decreased the mean area under the plasma concentration-time curve of glimepiride by 34% (P < 0.001) and the mean elimination half-life by 25% (P < 0.05). No significant differences in the blood glucose response to glimepiride were observed between the placebo and rifampicin phases. However, symptomatic hypoglycaemia occurred only during the placebo phase. CONCLUSIONS: The effects of rifampicin on the pharmacokinetics of glimepiride suggest that rifampicin induced the CYP2C9-mediated metabolism of glimepiride and thereby slightly increased its systemic clearance. Because the interaction was modest and did not significantly alter the glucose-lowering effect of glimepiride in healthy volunteers, it is probably of limited clinical significance. However, in some patients the hypoglycaemic effect of glimepiride may be reduced during concomitant treatment with rifampicin.

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