Effect of gemfibrozil on the pharmacokinetics and pharmacodynamics of glimepiride.
Author(s): Niemi M, Neuvonen PJ, Kivisto KT
Affiliation(s): Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Finland.
Publication date & source: 2001-11, Clin Pharmacol Ther., 70(5):439-45.
Publication type: Clinical Trial; Randomized Controlled Trial
OBJECTIVE: Our objective was to study the effects of gemfibrozil on the pharmacokinetics and pharmacodynamics of glimepiride, a new sulfonylurea antidiabetic drug and a substrate of cytochrome P4502C9 (CYP2C9). METHODS: In a randomized, 2-phase crossover study, 10 healthy volunteers were treated for 2 days with 600 mg oral gemfibrozil or placebo twice daily. On day 3, they received a single dose of 600 mg gemfibrozil or placebo and 1 hour later a single dose of 0.5 mg glimepiride orally. Plasma glimepiride, serum insulin, and blood glucose concentrations were measured up to 12 hours. RESULTS: Gemfibrozil increased the mean total area under the plasma concentration-time curve of glimepiride by 23% (range, 6%-56%; P <.005). The mean elimination half-life of glimepiride was prolonged from 2.1 to 2.3 hours (P <.05) by gemfibrozil. No statistically significant differences were found in the serum insulin or blood glucose variables between the two phases. CONCLUSIONS: Gemfibrozil modestly increases the plasma concentrations of glimepiride. This may be caused by inhibition of CYP2C9.