Abstract

MODULATORY EFFECTS OF SULFORAPHANE ON ERTUGLIFLOZIN PHARMACOKINETICS AND PHARMACODYNAMICS IN TYPE-2 DIABETIC RATS

Yellu Narsimha Reddy* and Meesa Madhavi

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Abstract

Sulforaphane (SFN), a bioactive compound derived from cruciferous vegetables, has demonstrated potential in improving insulin sensitivity and lipid profiles in diabetic models. Ertugliflozin(ERT), a sodiumglucose co-transporter 2 (SGLT2) inhibitor, is utilized to enhance glycemic control in type 2 diabetes mellitus (T2DM). This study mainly purposed to investigate the combined effects of SFN and ERT on the pharmacokinetics and pharmacodynamics in T2DM-induced rats. Rats were divided in to three groups, one group of rats were treated with ERT alone, second group rats were treated with SFN followed by ERT in single dose therapy, third group rats were treated with SFN followed by ERT in multidose therapy. Investigations were carried out by HPLC for pharmacokinetic study, blood glucose levels were estimated for pharmacodynamics study. SFN significantly decreased the maximum plasma concentration(Cmax), Area under curve(AUC), Mean residence time(MRT), Half-life (t1/2), Volume of distribution(Vd) and increased the clearance(CL) of ERT in multidrug therapy when compared to the ERT alone therapy. Pharmacodynamically ERT alone significantly reduced the blood glucose levels at 1.5h, SFN significantly decreased the blood glucose levels at 4h, but pre-treatment of SFN group slightly increased the blood glucose levels of ERT when compared to the ERT alone treated rats. These findings suggest that SFN may reduce the therapeutic efficacy of ERT in managing T2DM.

Keywords: Sulforaphane, Ertugliflozin, Area under Curve, HPLC.