Effect of gemfibrozil on the pharmacokinetics of mitiglinide in rats

A sensitive and specific method was developed and validated for the determination of mitiglinide in plasma using LC-MS/MS. The effect of gemfibrozil on the pharmacokinetics of orally administered mitiglinide in rats was investigated. The validated method in positive electrospray ionization mode using MRM and fully validated according to commonly accepted criteria. The desired sensitivity of mitiglinide was achieved with an LOQ of 0.5 ng/mL and the short run time was suitable for analysis of the large batches of samples. The method was successfully used to analyze rats plasma samples for application in pharmacokinetic studies. Pharmacokinetic parameters of mitiglinide were determined in rats following oral (0.25, 0.5, 1 mg/kg) administration to rats in the presence and absence of gemfibrozil (1 mg/kg). Compared to those animals in an oral control group (given mitiglinide alone), the area under the plasma concentration-time curve (AUC) of mitiglinide were increased significantly by 2.8, 3.5, 4.1-fold (0.25, 0.5, 1 mg/kg) by gemfibrozil, respectively. Consequently, the bioavailability of mitiglinide in the presence of gemfibrozil was significantly enhanced compared to that in oral control group (only mitiglinide). Gemfibrozil significantly enhanced the oral bioavailability of mitiglinide, suggesting that concurrent use of gemfibrozil and mitiglinide should be monitored closely for potential drug interactions.