Table 2.
Dolutegravir steady-state pharmacokinetic parameters and published adult reference pharmacokinetic parameters
| Pharmacokinetic visit at a median of 4.5 weeks on ART |
Pharmacokinetic visit at a median of 32 weeks on ART |
Adults ≥ 40 kg |
||||
|---|---|---|---|---|---|---|
| 50 mg QD | 50 mg BID | |||||
| (N=25) | (N=25) | (N=10)[1] | (N=23)[2, 3] | |||
| Parameter | GM (CV%) | Median (IQR) | GM (CV%) | Median (IQR) | GM (CV%)$ | GM (CV%)$ |
| T1/2 | 9.7 (29.6%) | 9.4 (8.3 – 11.2) | 9.5 (40.8) | 8.5 (7.4 – 11.0) | 12.0 (22%)a | |
| Tmax (h) | 3.2 (52.4%) | 4.0 (1.8 – 4.2) | 2.8 (62.8%) | 3.9 (1.0 – 4.1) | 2.0 (0.97-4.0)b | 2.0 (0-7.9)b |
| Cmax (mg/L) | 7.6 (40.1%) | 7.3 (5.8 – 9.7) | 7.0 (46.0%) | 7.0 (4.6 – 8.7) | 3.34 (16%)a | 5.41 (40%)a |
| C24h (mg/L) | 1.6 (52.7%) | 1.5 (1.3 – 2.3) | 1.4 (47.1%) | 1.4 (1.13 – 2.10) | 0.83 (26%) | 2.72 (70%)a |
| AUC0-24h (mg *h/mL) | 101.8 (37.7%) | 98.8 (86.8 – 138.2) | 88.6 (40.5%) | 86.6 (69.15 – 119.97) | 43.4 (20%) | 93.36 (50%)a |
| Vd/F (L) | 6.9 (52.3%) | 6.8 (4.0 – 9.3) | 7.8 (75.8%) | 7.0 (4.19 – 11.49) | ||
| CL/F (L/h) | 0.49 (46.6%) | 0.47 (0.35 – 0.57) | 0.56 (74.6%) | 0.51 (0.39 – 0.72) | 1.15 (20%)c | 0.54 (70%)c |
GM, geometric mean, CV, coefficient of variation, QD, once daily, BID, twice daily
$
GM (CV%) or otherwise specified
a
geometric mean (coefficient of variation)
b
median (range), T1/2, half-life, Tmax, time to peak concentration; Cmax, peak concentration; C24h, concentration at 24 hours post-dose, AUC0-24h, total area under the curve from time 0 hours to 24hours; Vd/F, apparent volume of distribution, CL/F, apparent oral clearance.