Effect of Diabetes mellitus on pharmacokinetics of metformin and telmisartan by using novel HPLC-UV method: A drug-disease interaction study

Metformin and Telmisartan are commonly co-prescribed drugs in diabetes plus hypertensive patients. Diabetes caused pharmacokinetic alterations in metformin due to alterations in drug metabolizing enzymes (DMEs) and/or transporters. But, there are no such reports for telmisartan alone or with metformin. Considering this, a simple, precise, robust, specific, and sensitive RP-HPLC method for simultaneous quantification of metformin and telmisartan in rat plasma were developed. Chromatographic separation achieved on cyano column with mobile phase consisting acetonitrile:10mM KH2PO4, pH 4.5 (60:40). Flow rate was 1.0mL/min. Detection wavelength was 237nm. The protein precipitation of both drugs from rat plasma was done using acetonitrile (recoveries ≥ 80%). HPLC bioanalytical calibration curve was found linear in the range of 10-3200ng/mL. Parameters like precision, accuracy, and stability were within accepted criteria for biomedical analysis. The developed method was successfully used for pharmacokinetic studies in normal and diabetic rats. Metformin (50mg/kg, p.o.; b.i.d.) and telmisartan (4mg/kg, p.o.; o.d.) were administered simultaneously. Diabetes significantly increased systemic exposure (increased AUC0 − t, Cmax; decreased CL, Vd) of metformin and telmisartan. This may be because of diabetes mediated increased SERT expression, decreased CYP2C11 and UGTs expression. Important to note that telmisartan doesn’t cause metformin PK alterations and vice-versa, in diabetic and normal rats.