Clinical pharmacokinetics on canagliflozin: a systematic review of in-vitro and in-vivo studies

Canagliflozin (CFZ), is a commonly used sodium-glucose cotransporter-2 inhibitor drug for the management of type 2 diabetes mellitus (T2DM). This review comprehensively compiles existing research studies regarding the clinical pharmacokinetic (PK) behavior of canagliflozin, primarily focusing on exploring effects of different disease conditions, potential drug interactions, and genetic polymorphism. A comprehensive review of scholarly literature was conducted by using leading databases, i.e. Google Scholar, Science Direct, PubMed, and Cochrane, to identify clinical PK studies of CFZ. The comprehensive literature search identified 25 articles that met the inclusion standards. A linear relationship was observed between the administered doses and PK parameters such as area under the curve from time 0 to infinity (AUC_0-∞) and maximum plasma concentration (C_max). The findings from T2DM patients with moderate renal impairment displayed a 27% increase in AUC_0-∞ of canagliflozin. Furthermore, co-administration of CFZ with rifampin in humans reduced Cmax by 28%, while with telmisartan in rats, CL/F decreased 31.1% initially, but increased 62.9% after 7 days. This review integrates all significant human PK parameters of CFZ by combining findings from existing studies, allowing researchers to develop and evaluate PK models for recommending model-based dose optimization. : CRD420251054714