Effect of gemfibrozil on the pharmacokinetics and pharmacodynamics of glimepiride.
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.
Niemi
M
M
Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Finland.
Neuvonen
P J
PJ
Kivistö
K T
KT
D000328:Adult; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases; D018592:Cross-Over Studies; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D004347:Drug Interactions; D005260:Female; D015248:Gemfibrozil / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008297:Male; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000502:physiology; D013453:Sulfonylurea Compounds / Q000493:pharmacokinetics* / Q000494:pharmacology
D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D013453:Sulfonylurea Compounds; C057619:glimepiride; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D039181:Steroid 16-alpha-Hydroxylase; D015248:Gemfibrozil