Currently, the total number of diabetic people worldwide is constantly increasing. Metformin (MET) is known to be a first-line antidiabetic drug with varied, wide-reaching applications. Concurrent administration of phytomedicines such as fenugreek extract with synthetic drugs is very common. It is reported that concomitant administration of fenugreek extract with metformin maintains lower blood glucose levels than metformin alone. In this work, an ecofriendly RP-HPLC method was established to study and compare the pharmacokinetics of metformin with and without the contemporary administration of fenugreek extract using rat as an animal model. In the developed method, a solvent mixture of 0.5 mM KH2PO4 solution : methanol (65 : 35, v/v) was used as a mobile phase and guaiphenesin was used as an internal standard. The plasma concentration-time curve was plotted, and non-compartmental pharmacokinetic analysis was performed using PKSolver. The results of the pharmacokinetic study showed that concurrent administration of fenugreek significantly increased the bioavailability of metformin and doubled the time required to reach the peak plasma concentration (T max). Moreover, the volume of drug distribution decreased by about 70%, while its rate of clearance decreased by about 55.96%. Accordingly, the administration of fenugreek in combination with metformin significantly affected the pharmacokinetics of metformin, and this combination will be very useful in controlling blood glucose levels in diabetic patients. The greenness of the method was assessed using the Analytical Eco-Scale, Analytical Method Volume Intensity (AMVI), and National Environmental Method Index (NEMI), and all results affirmed that the method can be considered to be ecological.
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