Table 2.
Pharmacokinetic parameters of dotinurad in plasma, with comparison between groups
| Parameters (unit) | Normal hepatic function (n = 6) | Mild hepatic impairment (n = 6) | ||
|---|---|---|---|---|
| Mean ± SD | Mean ± SD | Geometric mean ratioa | ||
| Point estimate | Two-sided 90% CI | |||
| Cmax (ng/mL) | 339.15 ± 28.57 | 289.88 ± 65.03 | 0.840 | 0.674–1.047 |
| Tmax (h) | 2.67 ± 1.03 | 2.17 ± 1.17 | – | – |
| T1/2 (h) | 10.80 ± 0.55 | 10.50 ± 2.42 | 0.953 | 0.792–1.147 |
| AUC0–48 (ng h/mL) | 4541.72 ± 343.39 | 4013.66 ± 823.02 | 0.869 | 0.693–1.091 |
| AUC0–inf (ng h/mL) | 4761.81 ± 369.35 | 4234.01 ± 950.16 | 0.872 | 0.684–1.112 |
| CLtot/F (L/h) | 0.844 ± 0.066 | 0.989 ± 0.240 | 1.147 | 0.900–1.463 |
| Vd/F (L) | 13.16 ± 1.19 | 14.52 ± 2.36 | 1.094 | 0.905–1.322 |
| Parameters (unit) | Moderate hepatic impairment (n = 9) | Severe hepatic impairment (n = 3) | ||||
|---|---|---|---|---|---|---|
| Mean ± SD | Geometric mean ratioa | Mean ± SD | Geometric mean ratioa | |||
| Point estimate | Two-sided 90% CI | Point estimate | Two-sided 90% CI | |||
| Cmax (ng/mL) | 280.34 ± 87.91 | 0.798 | 0.653–0.976 | 255.23 ± 46.06 | 0.747 | 0.570–0.979 |
| Tmax (h) | 2.44 ± 1.01 | – | – | 1.33 ± 0.58 | – | – |
| T1/2 (h) | 10.75 ± 2.28 | 0.978 | 0.826–1.158 | 9.82 ± 2.47 | 0.892 | 0.711–1.119 |
| AUC0–48 (ng h/mL) | 4095.91 ± 1133.49 | 0.875 | 0.711–1.077 | 3592.84 ± 1173.52 | 0.765 | 0.579–1.011 |
| AUC0–inf (ng h/mL) | 4327.09 ± 1249.48 | 0.879 | 0.704–1.098 | 3757.37 ± 1343.74 | 0.758 | 0.563–1.021 |
| CLtot/F (L/h) | 0.991 ± 0.262 | 1.137 | 0.911–1.420 | 1.159 ± 0.404 | 1.319 | 0.980–1.777 |
| Vd/F (L) | 14.99 ± 3.69 | 1.112 | 0.935–1.323 | 15.51 ± 1.97 | 1.177 | 0.933–1.485 |
AUC0–inf area under the plasma concentration − time curve from time 0 to infinity, AUC0–48 area under the plasma concentration − time curve from time 0 to 48 h, CI confidence interval, CLtot/F total clearance/fraction of dose absorbed, Cmax maximum plasma concentration, SD standard deviation, Tmax time to maximum plasma concentration, T1/2 elimination half-life, Vd/F distribution volume/fraction of dose absorbed
aThe mean was converted to a common logarithm and then the geometric mean ratio was calculated using the following formula:
Geometric mean ratio = 10Mean difference
Mean difference = (mean in the target group) − (mean in the normal hepatic function group)