High performance liquid chromatographic interaction studies of azithromycin and metformin in human plasma

Abstract

The work aimed at studying the interaction of azithromycin and metformin in human plasma using High/ performance Liquid Chromatography. Multiple drug therapy can give rise to drug interactions that can be of concern, because the outcome of concomitant drug administration could diminish therapeutic efficacy or increase the risk of toxicity of one or more of the administered drugs. Metformin and azithromycin are often prescribed in cases of diabetes with infections such as urinary tract infections. These provide several benefits to diabetic patients by reducing their blood sugar levels and protecting them from several infections without significant side effects. Six healthy volunteers with ages ranging from 40-60 years, weighing 45-75 kg participated in the study. Each of the six volunteers received metformin (1 g) tablet alone and 500 mg capsules of azithromycin concomitantly. Blood samples were collected at intervals of 0.0- 6.0, and 8.0 hours, from all the participants and kept at -4°C prior to analysis. Plasma was then extracted out from the blood samples so collected at 1:3 ratio of acetonitrile. The analysis for metformin was carried out using an adopted and validated HPLC method on a reversed phase column C-8, 4.6 x 150 nm, mobile phase acetonitrile/potassium hydrogen orthophosphate (21:79), and a UV detector at 236 nm. The pharmacokinetics of metformin were affected by the concomitant administration of azithromycin. Azithromycin decreased C_max and AUC to 1.13 μg/ml and 4.29 h (μg/ml/h) respectively, and reduced renal clearance by 16 %. The renal clearance of metformin was reduced in a time- dependent manner in the presence of azithromycin. Hence, it was concluded that azithromycin inhibits metformin renal tubular secretion, resulting in a higher circulating serum concentration. The study revealed pharmacokinetic changes of metformin when administered concomitantly with azithromycin. However, the changes were not significant (p > 0.05).