Table 3.
Descriptive Summarya of PF‐06481944 and PF‐06685948 Pharmacokinetic Parameter Values by Renal Function Group
| T2DM Subjects | ||||||
|---|---|---|---|---|---|---|
| PK Parametera | Normal Renal Function | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment | Healthy Subjects With Normal Renal Function | |
| PF‐06481944 | n | 6 | 8 | 8 | 6 | 8 |
| AUC, ng·h/mL | 1559 (21) | 2620 (34) | 3668 (56) | 2742 (41) | 1113 (32) | |
| Cmax, ng/mL | 218 (18) | 309 (30) | 359 (28) | 219 (33) | 169 (34) | |
| tmax, h | 2.00 (1.00‐3.00) | 2.00 (1.50‐4.00) | 3.00 (1.50‐3.00) | 3.00 (1.50‐4.00) | 2.00 (1.50‐3.00) | |
| t½, h | 16.7 ± 9.5 | 22.0 ± 12.2 | 23.3 ± 6.2 | 22.8 ± 5.9 | 17.5 ± 5.7 | |
| CLR, mL/min | 76.28 (24) | 38.73 (58) | 17.67 (56) | 10.27 (80) | 94.53 (25) | |
| MRAUCinf b | 0.93 (39) | 0.98 (45) | 1.26 (52) | 1.03 (37) | 0.64 (29) | |
| PF‐06685948 | n | 6 | 8 | 8 | 6 | 8 |
| AUC, ng·h/mL | 384 (26) | 604 (39) | 951 (75) | 975 (53) | 338 (27) | |
| Cmax, ng/mL | 44 (22) | 54 (17) | 63 (42) | 46 (35) | 44 (24) | |
| tmax, h | 2.00 (1.50‐3.00) | 3.00 (2.00‐4.03) | 4.00 (2.00‐4.00) | 3.51 (3.00‐4.02) | 2.00 (2.00‐3.00) | |
| t½, h | 14.9 ± 7.8 | 21.7 ± 11.3 | 22.5 ± 5.3 | 25.2 ± 10.4 | 15.7 ± 4.7 | |
| CLR, mL/min | 41.82 (24) | 22.50 (45) | 11.95 (49) | 5.78 (43) | 41.42 (31) | |
| MRAUCinf | 0.23 (34) | 0.23 (35) | 0.33 (82) | 0.37 (36) | 0.19 (25) | |
Normal renal function, eGFR ≥90 mL/min; mild renal impairment, eGFR 60‐89 mL/min; moderate renal impairment, eGFR 30–59 mL/min; severe renal impairment eGFR <30 mL/min. %CV, percentage coefficient of variation; AUC, area under the plasma concentration‐time profile from time 0 extrapolated to infinite time; CLR, renal clearance; Cmax, maximum observed concentration; h, hour; MRAUCinf, metabolite‐to‐parent ratio for AUC; n, number of subjects; SD, standard deviation; tmax, time for Cmax; t½, terminal half‐life.
aGeometric mean (geometric %CV) for all except median (range) for tmax and arithmetic mean (±SD) for t½.
bPF‐06481944 and PF‐06685948 data are corrected for molecular weight (ng to nmol; molecular weight = 613.01 for both). Ertugliflozin data are corrected for molecular weight (ng to nmol; molecular weight = 463.88).