Table 2.
Comparison and Summary of Dolutegravir Pharmacokinetic Parameters and Unbound Concentrations
| Parameter | Hepatic Impaired (Dolutegravir 50 mg, n = 8)a | Healthy (Dolutegravir 50 mg, n = 8)a | Hepatic Impaired vs. Healthy, GLS Mean Ratio (90% CI)b |
|---|---|---|---|
| Cmax, µg/mL | 1.18 (0.29) | 1.97 (0.86) | 1.02 (0.754, 1.37) |
| C24, µg/mL | 0.62 (0.26) | 0.61 (0.22) | 1.04 (0.727, 1.48) |
| AUC(0–∞), µg h/mL | 40.0 (13.0) | 40.3 (15.1) | 1.05 (0.745, 1.49) |
| CL/F, L/h | 1.34 (0.36) | 1.48 (0.77) | 0.950 (0.673, 1.34) |
| Vz/F, L | 29.4 (5.11) | 31.6 (14.8) | 0.986 (0.737, 1.32) |
| t1/2, h | 15.8 (3.11) | 15.3 (3.93) | 1.04 (0.845, 1.27) |
| tmax, h | 4.00 (2.0–5.0) | 3.00 (1.0–4.0) | 1.00 (−0.500, 2.50) |
| Unbound dolutegravir concentration at 3 h, ng/mL | 8.38 (3.22) | 4.51 (2.44) | 2.062 (1.404, 3.029) |
| Unbound dolutegravir concentration at 24 h, ng/mL | 2.49 (0.58) | 1.19 (0.75) | 1.483 (1.217, 1.807) |
| Unbound fraction at 3 h, % | 0.54 (0.19) | 0.23 (0.04) | 2.20 (1.62, 2.99) |
| Unbound fraction at 24 h, % | 0.44 (0.14) | 0.23 (0.03) | 1.76 (1.23, 2.51) |
AUC(0–∞), area under the plasma concentration-time curve from time zero to infinity; C24, concentration at 24 hours post-dose; CI, confidence interval; CL/F, apparent oral clearance; Cmax, maximum observed plasma concentration; GLS, geometric least squares; t1/2, half-life; Tmax, time to Cmax; Vz/F, apparent volume of distribution after extravascular administration.
a
Data are arithmetic mean and standard deviation, except for Tmax, which is median (range).
b
Data are GLS mean ratio (90% CI) except for Tmax, which is Hodges–Lehmann estimate of difference (90% CI).