*3.2. Pharmacokinetics and Kidney Distribution of DWP16001, Dapagliflozin, and Ipragliflozin in Mice*

To compare the pharmacokinetic profile of DWP16001 with those of dapagliflozin and ipragliflozin, the same dose of the three SGLT2 inhibitors was orally administered to ICR mice (1 mg/kg each), and the concentrations of DWP16001, dapagliflozin, and ipragliflozin in plasma and kidney samples were analyzed. The PK profiles of DWP16001, dapagliflozin, and ipragliflozin are shown in Figure 4 and the PK parameters were summarized in Table 1.

● ▼ ○ **Figure 4.** (**A**) Plasma and (**B**) kidney concentration vs. time profile of DWP16001 (•), dapagliflozin (H), and ipragliflozin (#) after a single oral administrations of DWP16001, dapagliflozin, and ipragliflozin at a dose of 1 mg/kg in Institute of Cancer Research (ICR) mice, respectively. Data are expressed as mean±SD from five mice.

**Table 1.** Pharmacokinetic parameters of DWP16001, dapagliflozin, and ipragliflozin after a single oral administrations of DWP16001, dapagliflozin, and ipragliflozin at a dose of 1 mg/kg in ICR mice, respectively.


Area under curve (AUC) ratio: Ratios of Kidney AUC to plasma AUC; Data expressed as mean ± SD from five mice; \*: *p* < 0.05, compared with DWP16001 group.

As shown in Figure 4, plasma concentrations of DWP16001 were similar to those of ipragliflozin and greater than those of dapagliflozin. Consequently, the AUC and Cmax values of DWP16001 were similar to those of ipragliflozin and higher than those of dapagliflozin. However, the concentrations of DWP16001 in the kidney were maintained at higher concentrations for 72 h compared with those of ipragliflozin and dapagliflozin, suggesting the prolonged efficacy of DWP16001 via the inhibition of SGLT2, which is located in the renal proximal tubule [3]. Because of the high and prolonged concentration of DWP16001, the AUC, AUC ratio, and t1/<sup>2</sup> values of DWP16001 were significantly greater than those of dapagliflozin and ipragliflozin (Table 1).
