Table 3.
Plasma PK parameters of unbound letermovir at steady state in subjects with moderate and severe hepatic impairment and matched healthy control subjects
| Moderate hepatic impairment (n = 8) | Healthy (moderate impairment matched) controls (n = 8) | Severe hepatic impairment (n = 8a) | Healthy (severe impairment matched) controls (n = 8a) | |||||
|---|---|---|---|---|---|---|---|---|
| AUC τ,ss, ng.h ml −1 | 141.30 ± 125.30 | 66.93 ± 31.91 | 155.40 ± 94.91 | 26.58 ± 6.61 | ||||
| C ss,av, ng ml −1 | 5.885 ± 5.217 | 2.79 ± 1.33 | 6.47 ± 3.95 | 1.11 ± 0.28 | ||||
| C ss,max, ng ml −1 | 18.86 ± 9.548 | 12.93 ± 6.64 | 17.67 ± 10.67 | 5.05 ± 1.62 | ||||
| C min, ng ml −1 | 1.79 ± 2.83 | 0.63 ± 0.43 | 1.84 ± 0.79 | 0.19 ± 0.11 | ||||
| LS means | LS means | |||||||
|---|---|---|---|---|---|---|---|---|
| Moderate hepatic impairment | Matched healthy subjects | LS means ratio % (90% CI) | P valueb | Severe hepatic impairment | Matched healthy subjects | LS means ratio % (90% CI) | P valueb | |
| AUC τ,ss, ng.h ml −1 | 108.3 | 59.72 | 181.4 (102.8–320.0) | 0.0860 | 138.8 | 25.88 | 536.2 (386.3–744.4) | <0.0001 |
| C ss,max, ng ml −1 | 17.11 | 10.94 | 156.4 (92.96–263.3) | 0.1521 | 15.88 | 4.831 | 328.7 (233.2–463.2) | <0.0001 |
AUCτ,ss, area under the concentration vs. time curve over a dosing interval at steady state; Cmin, minimal observed concentration; Css,av, average steady‐state concentration over the dosing interval; Css,max, maximal observed concentration at steady state; CI, confidence interval; LS, least square; PK, pharmacokinetic
Dosing interval (τ) = 24 h. All data are mean ± standard deviation.
a
n = 6 for λz, t1/2z and Vss/F.
b
P values were calculated using an analysis of variance model with the logarithm of PK parameters as dependent variable and hepatic status as fixed effect.