PloS one · 2026
Pharmacokinetic interactions between three SGLT2 inhibitors and telmisartan: A focus on empagliflozin, ertugliflozin, and henagliflozin.
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Zhou Xin, Deng Yanru, Guo Caihui, Li Ying, Fu Yuhao, Wang Zhi, Dong Zhanjun
Аннотация
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 AUC0-t, AUC0-∞ and Cmax of henagliflozin and decreased the CLz/F(all p ＜ 0.05). When coadministered with ertugliflozin or henagliflozin, the AUC0-t and AUC0-∞ of telmisartan decreased significantly and the CLz/F increased significantly(all p ＜ 0.05). Furthermore, PCR results demonstrated that telmisartan decreased the expression of BCRP expression in liver, intestines and kidney, P-gp expression in the intestines and kidney and OATP1B2 expression in liver tissue.
CONCLUSIONS: Our findings highlight the importance of these drug interactions, which could inform dose adjustments to enhance safety in patients with T2DM and hypertension.
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 AUC0-t, AUC0-∞ and Cmax of henagliflozin and decreased the CLz/F(all p ＜ 0.05). When coadministered with ertugliflozin or henagliflozin, the AUC0-t and AUC0-∞ of telmisartan decreased significantly and the CLz/F increased significantly(all p ＜ 0.05). Furthermore, PCR results demonstrated that telmisartan decreased the expression of BCRP expression in liver, intestines and kidney, P-gp expression in the intestines and kidney and OATP1B2 expression in liver tissue.
CONCLUSIONS: Our findings highlight the importance of these drug interactions, which could inform dose adjustments to enhance safety in patients with T2DM and hypertension.