TABLE 2.
HIV antiretroviral drug pharmacokinetic properties
| Parameter | Value(s) for: |
||||||||
|---|---|---|---|---|---|---|---|---|---|
| Dolutegravir |
Abacavir |
Lamivudine |
|||||||
| Period 1, day 7 (n = 12) | With 3-direct-acting-antiviral regimen, period 2, day 24 (n = 11) | Ratios of central valuesa (90% CIs) | With lamivudine, period 1, day 4 (n = 12) | With lamivudine and 3-direct-acting-antiviral regimen, period 2, day 24 (n = 11) | Ratios of central valuesa (90% CIs) | With abacavir, period 1, day 4 (n = 12) | With abacavir and 3-direct-acting-antiviral regimen, period 2, day 24 (n = 11) | Ratios of central valuesa (90% CIs) | |
| Cmax, ng/mlb | 5,290 (15.8) | 6,560 (18.5) | 1.219 (1.153, 1.288) | 5,080 (23.5) | 4,460 (26.9) | 0.873 (0.777, 0.979) | 2,720 (33.7) | 2,120 (27.6) | 0.778 (0.719, 0.842) |
| Tmax, hc | 3.0 (1.0, 6.0) | 3.0 (1.0, 4.0) | 1.3 (1.0, 2.0) | 1.5 (1.0, 2.0) | 2.0 (1.0, 4.0) | 2.0 (1.0, 4.0) | |||
| AUC24, ng · h/mlb | 66,600 (17.0) | 93,700 (17.0) | 1.380 (1.295, 1.469) | 17,100 (27.5) | 16,500 (28.4) | 0.943 (0.901, 0.986) | 15,000 (23.7) | 13,200 (23.7) | 0.876 (0.821, 0.934) |
| Ctrough, ng/mlb | 1,500 (24.0) | 2,100 (20.3) | 1.357 (1.190, 1.548) | 12.9e (279) | 15.6f (226) | NDg | 62.7 (25.4) | 88.0 (30.6) | 1.287 (1.050, 1.578)i |
| t1/2, hd | 15.5 (1.87) | 12.6 (1.87) | 2.26 (0.46) | 2.98 (0.94) | 14.1 (10.3) | 13.7 (4.7) | |||
Values shown are ratios of central values (90% CIs) for ART plus the 3-direct-acting-antiviral regimen versus ART alone. Data are point estimates (90% confidence intervals). Point estimates are derived from the antilogarithm of the difference of the least-squares means for logarithms.
Geometric mean (percent coefficient of variation).
Median (range).
Harmonic mean (pseudostandard deviation).
Eight subjects had concentrations below the lower limit of quantitation.
Two subjects had concentrations below the lower limit of quantitation.
ND, not done. The effect of the 3-direct-acting antiviral regimen on abacavir Ctrough could not be estimated, as abacavir Ctrough concentration was below the lower limit of quantification in the majority of subjects in period 1.
For period 2, only data up to 48 h postdose were used for half-life determination.
One subject was excluded from the Ctrough analysis for lamivudine.