Pharmacokinetic interactions between three SGLT2 inhibitors and telmisartan: A focus on empagliflozin, ertugliflozin, and henagliflozin
Abstract
Background: Patients with type 2 diabetes mellitus (T2DM) usually accompany with the occurrence of high blood pressure, necessitating a combination of treatments. This includes sodium-glucose co-transporter 2(SGLT2) inhibitors like empagliflozin, ertugliflozin, and henagliflozin, and antihypertensives like telmisartan. Both classes interact with transporters like P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), with telmisartan further inhibiting several, including organic anion transporting poly-peptide (OATP) 1B1/1B3.
Objective: Despite their common use, pharmacokinetic interactions between these drugs remain underexplored. This study aims to investigate the potential pharmacokinetic interaction between three specific SGLT2 inhibitors and telmisartan.
Methods: Rats were divided into twelve groups, with six rats per group, and received different combinations of empagliflozin, ertugliflozin, henagliflozin, and telmisartan. Drug concentrations were measured using ultra-performance liquid chromatography-tandem mass spectrometry, and mRNA expressions through quantitative reverse transcription polymerase chain reaction (RT-qPCR).
Results: Our study manifested that telmisartan increased the plasma concentration-time curves (AUC0-t and AUC0-∞) and the maximum plasma concentrations (Cmax) of empagliflozin, whereas the apparent clearance (CLz/F) and apparent volume of distribution (Vz) significantly decreased(all p ＜ 0.05). Similarly, telmisartan increased the…
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