Sergliflozin (S) is a selective inhibitor of the sodium-glucose cotransporter2 (SGLT2) expressed on the luminal side of the renal proximal tubule epithelium. S produces concentration-dependent urine glucose excretion (UGE) in humans. Modeling objectives were to understand human pharmacology and to optimize dose selection for effective plasma glucose reduction. The use of a competitive inhibition model was substantiated by in vitro pharmacology data, where the drug competes with glucose at the SGLT2 transporter. Inhibition, expressed as UGE, is a function of renal tubule concentrations and dissociation rate constants of both the drug and glucose. Proximal renal tubule concentrations of drag and glucose are estimated from circulating unbound plasma concentrations. The plot shows good in vivo/in vitro association between human UGE data from S administration and predicted inhibition. It is apparent that 50-90% inhibition of transporter is needed to elicit a clinical response in both normoglycemic (•) and diabetic (Δ) patients. The extent of SGLT2 inhibition can be used to calculate effective plasma drug concentrations and doses for larger long-term clinical studies. [ABSTRACT FROM AUTHOR]