Table 2.
Plasma pharmacokinetic parameters of verinurad, metabolite M1, and metabolite M8 following verinurad 15 mg administration in subjects with normal renal function and mild, moderate, and severe renal impairment
| Parameter | Renal function | |||||
|---|---|---|---|---|---|---|
| Normal (N = 8) | Mild impairment (N = 8) | Moderate impairment (N = 7) | Severe impairment (N = 7) | |||
| Verinurad | Cmax (ng/ml) | GM (95% CI) | 16.7 (12.6–22.3) | 25.6 (20.0–32.9) | 29.0 (22.8–37.0) | 38.2 (24.0–60.8) |
| GLSMR (90% CI) | – | 153% (115–203) | 173% (131–230) | 228% (155–336) | ||
| AUC0–∞ (ng·h/ml) | GM (95% CI) | 162 (120–218) | 201 (144–279) | 402 (255–634) | 372 (209–663) | |
| GLSMR (90% CI) | – | 124% (88.8–173) | 248% (168–366) | 230% (146–363) | ||
| Tmax (h), median (range) | GM (95% CI) | 2.50 (0.500–4.00) | 2.50 (1.00–4.00) | 3.00 (1.50–5.00) | 2.00 (1.50–4.00) | |
| GLSMR (90% CI) | – | NA | NA | NA | ||
| t½ (h) | GM (95% CI) | 13.0 (7.91–21.5) | 9.53 (7.42–12.2) | 20.6 (9.96–42.4) | 22.0 (14.2–34.1) | |
| GLSMR (90% CI) | – | NA | NA | NA | ||
| CL/F (L/h) | GM (95% CI) | 92.6 (68.7–125) | 74.8 (53.7–104) | 37.3 (23.7–58.9) | 40.3 (22.6–71.7) | |
| GLSMR (90% CI) | – | 80.8% (57.9–113) | 40.3% (27.3–59.5) | 43.5% (27.5–68.7) | ||
| M1 | Cmax (ng/ml) | GM (95% CI) | 25.7 (19.9–33.3) | 33.3 (24.0–46.3) | 54.6 (44.3–67.3) | 91.0 (65.8–126) |
| GLSMR (90% CI) | – | 129% (94.9–177) | 212% (165–273) | 353% (262–478) | ||
| AUC0–∞ (ng·h/ml) | GM (95% CI) | 233 (175–310) | 266 (172–412) | 727 (495–1070) | 969 (533–1760) | |
| GLSMR (90% CI) | – | 115% (77.6–169) | 313% (221–442) | 416% (262–662) | ||
| Tmax (h), median (range) | GM (95% CI) | 2.50 (1.50–4.00) | 3.00 (1.00–4.00) | 2.00 (1.50–6.00) | 2.00 (1.50–2.00) | |
| GLSMR (90% CI) | – | NA | NA | NA | ||
| t½ (h) | GM (95% CI) | 11.9 (6.61–21.3) | 10.6 (6.72–16.8) | 20.8 (10.9–39.8) | 21.2 (11.8–38.0) | |
| GLSMR (90% CI) | – | NA | NA | NA | ||
| CL/F (L/h) | GM (95% CI) | NA | NA | NA | NA | |
| GLSMR (90% CI) | – | NA | NA | NA | ||
| M8 | Cmax (ng/ml) | GM (95% CI) | 23.6 (19.5–28.5) | 37.2 (28.1–49.1) | 36.9 (22.8–59.7) | 87.2 (70.0–109) |
| GLSMR (90% CI) | – | 158% (123–203) | 156% (109–224) | 370% (299–458) | ||
| AUC0–∞ (ng·h/ml) | GM (95% CI) | 250 (195–320) | 339 (242–476) | 601 (324–1110) | 1570 (902–2720) | |
| GLSMR (90% CI) | – | 136% (99.3–186) | 241% (152–382) | 627% (411–956) | ||
| Tmax (h), median (range) | GM (95% CI) | 3.50 (2.00–5.00) | 3.00 (1.50–4.00) | 3.00 (2.00–6.00) | 3.00 (2.00–5.00) | |
| GLSMR (90% CI) | – | 136% (99.3–186) | 241% (152–382) | 627% (411–956) | ||
| t½ (h) | GM (95% CI) | 14.4 (8.62–24.0) | 10.7 (8.47–13.4) | 23.2 (14.0–38.4) | 22.8 (13.7–37.9) | |
| GLSMR (90% CI) | – | NA | NA | NA | ||
| CL/F (L/h) | GM (95% CI) | NA | NA | NA | NA | |
| GLSMR (90% CI) | – | NA | NA | NA | ||
AUC0–∞ area under the concentration–time curve from time zero to infinity, CI confidence interval, CL/F total body clearance, Cmax maximum observed concentration, GLSMR geometric least squares mean ratio versus normal renal function group, GM geometric mean, NA not applicable, t½ terminal half-life, Tmax time of maximum observed concentration