Lack of effect of bezafibrate and fenofibrate on the pharmacokinetics and pharmacodynamics of repaglinide.
OBJECTIVE
Gemfibrozil markedly increases the plasma concentrations and blood glucose-lowering effects of repaglinide, but the effects of other fibrates on repaglinide pharmacokinetics are not known. Our aim was to investigate the effects of bezafibrate and fenofibrate on the pharmacokinetics and pharmacodynamics of repaglinide.


METHODS
In a randomized, three-phase cross-over study, 12 healthy subjects received 400 mg bezafibrate, 200 mg fenofibrate or placebo once daily for 5 days. On day 5, a single 0.25 mg dose of repaglinide was ingested 1 h after the last pretreatment dose. The concentrations of plasma repaglinide, bezafibrate and fenofibrate and blood glucose were measured up to 7 h postdose.


RESULTS
During the bezafibrate and fenofibrate phases, the total area under the concentration-time curve [AUC(0, infinity )] of repaglinide was 99% (95% confidence interval of the ratio to the control phase 73, 143%) and 99% (85, 127%) of the corresponding value during the placebo (control) phase, respectively. Bezafibrate and fenofibrate had no significant effect on the peak concentration (Cmax) of repaglinide. The mean half-life of repaglinide was 1.3 h in all phases. The blood glucose-lowering effect of repaglinide was not affected by bezafibrate or fenofibrate. The AUC(0,8 h) values for bezafibrate and fenofibrate varied 3.0-fold and 4.4-fold between individual subjects, respectively. Neither bezafibrate nor fenofibrate affected the pharmacokinetic variables of repaglinide.


CONCLUSIONS
Bezafibrate and fenofibrate do not affect the pharmacokinetics or pharmacodynamics of repaglinide.
Kajosaari
Lauri I
LI
Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
Backman
Janne T
JT
Neuvonen
Mikko
M
Laitila
Jouko
J
Neuvonen
Pertti J
PJ
D000328:Adult; D001629:Bezafibrate / Q000008:administration & dosage / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D002219:Carbamates / Q000008:administration & dosage / Q000494:pharmacology*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004347:Drug Interactions; D011345:Fenofibrate / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D013607:Tablets
D001786:Blood Glucose; D002219:Carbamates; D003692:Delayed-Action Preparations; D000960:Hypolipidemic Agents; D010880:Piperidines; D013607:Tablets; C072379:repaglinide; D011345:Fenofibrate; D001629:Bezafibrate