Drug-drug interactions of gemfibrozil and rosiglitazone-Indian study.

      Аннотация: The study designed to investigate the effect of gemfibrozil on the pharmacokinetics of rosiglitazone in Indian healthy adult male volunteers. This prospective open label randomized two-way crossover study was conducted in 12 Indian healthy adult male volunteers after ethical committee approval. Rosiglitazone 4mg tablet was administered either with or without pre-treatment of gemfibrozil 600mg tablets twice daily for 3 days. Plasma drug concentrations from time 0 to 12 hours were estimated by validated HPLC-UV method. The pharmacokinetic parameters were calculated and compared for statistical significance and 95% confidence interval (CI). Gemfibrozil increased the bioavailability of rosiglitazone to the extent comparable with the reports found in literature. But the increased bioavailability of rosiglitazone even without interacting drug enhanced the risk of concentration dependent adverse effects of rosiglitazone in Indian subjects. This was further augmented by co-administration of gemfibrozil. These findings supported the regulator’s recent decision to ban the drug in the country.

Ключевые слова: Pharmacokinetics, Healthy volunteers, Rosiglitazone, Gemfibrozil, Drug- drug Interactions