Evaluation of influence of telmisartan on the pharmacokinetics and tissue distribution of canagliflozin in rats and mice.

Abstract

Canagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, is widely used for the treatment of type 2 diabetes mellitus. However, drug interactions with canagliflozin can affect its glucoselowering therapeutic effects or exacerbate its adverse effects. Telmisartan, an angiotensin receptor blocker (ARB), has been approved for the treatment of diabetic kidney disease. This study aimed to investigate the effects of telmisartan on the pharmacokinetics and tissue distribution of canagliflozin. An ultra-performance liquid chromatography-tandem mass spectrometry method was successfully validated to determine the levels of canagliflozin in the plasma and tissues. The main pharmacokinetic parameters were calculated using the non-compartmental model. Compared with animals administered canagliflozin alone, the area under the receiver operating characteristic curve of animals co-administered telmisartan and canagliflozin was significantly increased after a single-day administration, but significantly decreased after a seven-day treatment regimen (both P<0.05). The highest concentrations of canagliflozin were detected in the kidneys, followed by the intestine, liver, heart, lung, spleen, and brain tissues. Furthermore, the concentration of canagliflozin in the heart, liver, lung, and kidney tissues at 2 hours post-administration was significantly higher in the telmisartan and canagliflozin group compared to the group treated with canagliflozin alone (P<0.05). A pharmacokinetic drug-drug interaction between telmisartan and canagliflozin might occur during drug co-administration.