Table 3.
Urinary 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 | CLR0–72 (ml/min) | GM (95% CI) | 13.5 (9.03–20.2) | 12.9 (8.16–20.4) | 7.87 (3.36–18.4) | 2.86 (1.84–4.45) |
| GLSMR (90% CI) | – | 95.4% (60.6–150) | 58.3% (30.2–113) | 21.2% (13.6–32.8) | ||
| fe0–72 (%) | GM (95% CI) | 0.814 (0.508–1.31) | 1.02 (0.563–1.84 | 1.05 (0.561–1.96) | 0.362 (0.202–0.647) | |
| GLSMR (90% CI) | – | NA | NA | NA | ||
| M1 | CLR0–72 (ml/min) | GM (95% CI) | 201 (168–240) | 163 (108–245) | 80.4 (51.0–127) | 19.6 (14.4–26.7) |
| GLSMR (90% CI) | – | 81.0% (58.2–113) | 40.0% (28.5–56.1) | 9.78% (7.60–12.6) | ||
| fe0–72 (%) | GM (95% CI) | 11.7 (8.83–15.4) | 11.2 (7.87–16.0) | 13.1 (9.08–18.8) | 4.32 (2.71–6.88) | |
| GLSMR (90% CI) | – | NA | NA | NA | ||
| M8 | CLR0–72 (ml/min) | GM (95% CI) | 298 (255–347) | 220 (158–307) | 117 (82.4–167) | 35.0 (23.6–52.0) |
| GLSMR (90% CI) | – | 73.9% (56.3–97.0) | 39.5% (30.2–51.6) | 11.8% (8.77–15.8) | ||
| fe0–72 (%) | GM (95% CI) | 18.0 (13.8–23.4) | 18.8 (14.6–24.3) | 15.0 (8.32–26.9) | 11.9 (7.73–18.4) | |
| GLSMR (90% CI) | – | NA | NA | NA | ||
CI confidence interval, CLR0–72 renal clearance in urine from time zero to 72 h, fe0–72 fraction of drug excreted in urine unchanged from time zero to 72 h; GLSMR geometric least squares mean ratio versus normal renal function group, GM geometric mean, NA not applicable