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my personal edition > diabetes > news
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DGReview
Repaglinide Potency Greatly Increased When Combined With Gemfibrozil
A DGReview of :"Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics and pharmacodynamics of repaglinide: potentially hazardous interaction between gemfibrozil and repaglinide"
Diabetologia
04/24/2003
By David Loshak
A potentially hazardous interaction between gemfibrozil, a fibrate, and repaglinide, an oral hypoglycaemic agent, has been found by Finnish specialists.
Gemfibrozil, especially in combination with itraconazole, greatly increased and prolonged the blood glucose-lowering effect of repaglinide, they found. Repaglinide thus became a long-acting and stronger anti-diabetic.
Clinicians should avoid using the two medications together, the specialists warned. If the combination is necessary, repaglinide dosage should be greatly reduced and blood glucose concentrations carefully monitored.
The specialists, clinical pharmacologists at Helsinki University Central Hospital, Finland, studied possible interactions of gemfibrozil, itraconazole and their combination with repaglinide in a randomised crossover study.
They enrolled 12 healthy volunteers who were given either gemfibrozil 600 mg., itraconazole 100 mg. (first dose 200 mg.), gemfibrozil and itraconazole together or placebo, all twice daily for 3 days. On the third day, the volunteers took a 0.25 mg. dose of repaglinide.
Plasma drug and blood glucose concentrations were followed for 7 hours and serum insulin and C-peptide concentrations for 3 hours post-dose.
Gemfibrozil raised the area under the plasma concentration-time curve of repaglinide by 5.5-15.0 times and prolonged its half-life from 1.3 to 3.7 hours.
Itraconazole alone raised repaglinide's area under the plasma concentration-time curve by 1.1-1.9 times. But, the gemfibrozil-itraconazole combination raised it by 12.9-24.7 times and prolonged repaglinide's half-life to 6.1 hours.
Gemfibrozil increased plasma repaglinide concentration at 7 hours by 28.6 times. The gemfibrozil-itraconazole combination increased plasma repaglinide concentration at 7 hours by 70.4 times.
Diabetologia 2003;46:347-351.
"Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics and pharmacodynamics of repaglinide: potentially hazardous interaction between gemfibrozil and repaglinide"
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