Repaglinide-gemfibrozil drug interaction: inhibition of repaglinide glucuronidation as a potential additional contributing mechanism

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Dose-dependent interaction between gemfibrozil and repaglinide in humans: strong inhibition of CYP2C8 with subtherapeutic gemfibrozil doses.

Gemfibrozil 1-O-β-glucuronide inactivates CYP2C8 irreversibly. We investigated the effect of gemfibrozil dose on CYP2C8 activity in humans using repaglinide as a probe drug. In a randomized, five-phase crossover study, 10 healthy volunteers ingested 0.25 mg of repaglinide 1 h after different doses of gemfibrozil or placebo. Concentrations of plasma repaglinide, gemfibrozil, their metabolites, a...

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Electrochemical determination of the antidiabetic drug repaglinide.

The electrochemical oxidation of repaglinide has been carried out in Britton-Robinson buffer at carbon paste and glassy carbon electrodes. Repaglinide exhibits a well-defined irreversible oxidation peak over the entire pH range (2-11). Differential pulse voltammetry was used to determine repaglinide in pure form. The peak current varied linearly in the following ranges: 8.0 x 10(-7)-3.2 x 10(-6...

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Dmd049460 362..371

The plasma concentration of repaglinide is reported to increase greatly when given after repeated oral administration of itraconazole and gemfibrozil. The present study analyzed this interaction based on a physiologically based pharmacokinetic (PBPK) model incorporating inhibition of the hepatic uptake transporter and metabolic enzymes involved in repaglinide disposition. Firstly, the plasma co...

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Hypersensitivity to repaglinide.

Meglitinides (repaglinide and nateglinide) are insulin secretagogues used to treat diabetes mellitus. We present a case of hypersensitivity reaction to repaglinide in a 61-year-old man who developed a maculopapular rash 5 days after treatment. Skin prick tests including repaglinide (0.5 g/mL) and patch tests (0.05% in pet and saline) were performed, and the results were negative. A blind oral c...

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CYP2C8 activity recovers within 96 hours after gemfibrozil dosing: estimation of CYP2C8 half-life using repaglinide as an in vivo probe.

Gemfibrozil 1-O-beta-glucuronide is a mechanism-based inhibitor of cytochrome P450 2C8. We studied the recovery of CYP2C8 activity after discontinuation of gemfibrozil treatment using repaglinide as a probe drug, to estimate the in vivo turnover half-life of CYP2C8. In a randomized five-phase crossover study, nine healthy volunteers ingested 0.25 mg of repaglinide alone or after different time ...

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ژورنال

عنوان ژورنال: British Journal of Clinical Pharmacology

سال: 2010

ISSN: 0306-5251

DOI: 10.1111/j.1365-2125.2010.03772.x