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Effect of gemfibrozil on the pharmacokinetics and pharmacodynamics of glimepiride
Author(s) -
Niemi Mikko,
Neuvonen Pertti J.,
Kivistö Kari T.
Publication year - 2001
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(01)84578-1
Subject(s) - glimepiride , gemfibrozil , pharmacokinetics , pharmacodynamics , medicine , pharmacology , crossover study , placebo , endocrinology , type 2 diabetes , diabetes mellitus , cholesterol , alternative medicine , pathology
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. Clinical Pharmacology & Therapeutics (2001) 70 , 439–445; doi: 10.1016/S0009‐9236(01)84578‐1