Table 3.
Plasma GSK’254 PK Parameters After Single- and Repeat-Dose Administration
| Geometric mean, (% CVb)a | GSK’254 10 mg (n = 6) |
GSK’254 40 mg (n = 6) |
GSK’254 80 mg (n = 6) |
GSK’254 140 mg (n = 6) |
GSK’254 200 mg (n = 6)b |
|---|---|---|---|---|---|
| Day 1 | |||||
| AUC0-24, µg∗h/mL | 0.70 (13.5) | 3.25 (31.7) | 6.12 (38.8) | 14.0 (36.6) | 12.40 (91.3) |
| 95% CI | .59–.82 | 2.35–4.50 | 4.13–9.07 | 9.67–20.40 | 5.48–28.00 |
| Range | 0.59–0.81 | 2.41–5.60 | 3.80–11.20 | 10.15–23.82 | 2.69–23.20 |
| Cmax, µg/mL | 0.06 (177.4) | 0.23 (30.5) | 0.43 (33.6) | 0.92 (41.5) | 0.94 (82.3) |
| 95% CI | .02–.21 | .17–.32 | .31–.61 | .60–1.40 | .44–2.00 |
| Range | 0.02–0.55 | 0.17–0.40 | 0.29–0.75 | 0.58–1.80 | 0.23–1.53 |
| tmax, median (range), h | 2.93 (0.00–5.00) | 4.42 (3.97–8.00) | 4.08 (2.95–6.17) | 5.51 (3.00–6.25) | 5.53 (3.92–8.05) |
| Day 8, 9, or 10 (part 1) or day 7 (part 2) | |||||
| AUC0-τ, µg∗h/mL | 0.91 (44.7) | 7.46 (26.8) | 11.80 (26.7) | 29.30 (27.9) | 27.90 (18.4) |
| 95% CI | .58–1.42 | 5.66–9.84 | 8.98–15.60 | 22.00–39.00 | 23.10–33.80 |
| Range | 0.41–1.33 | 5.76–11.47 | 8.96–16.68 | 17.76–37.70 | 22.27–34.79 |
| Cmax, µg/mL | 0.06 (41.3) | 0.47 (20.6) | 0.75 (23.7) | 1.86 (26.0) | 1.86 (19.5) |
| 95% CI | .04–.08 | .38–.58 | .59–.96 | 1.42–2.43 | 1.51–2.27 |
| Range | 0.03–0.08 | 0.35–0.61 | 0.60–1.13 | 1.17–2.52 | 1.43–2.45 |
| tmax, median (range), h | 4.02 (1.87–5.00) | 4.06 (2.00–8.00) | 4.58 (4.00–5.18) | 4.08 (2.92–5.20) | 5.48 (3.00–6.20) |
| Cτ, µg/mL | 0.03 (47.0) | 0.22 (30.1) | 0.36 (31.1) | 0.80 (34.1) | 0.70 (29.6) |
| 95% CI | .02–.04 | .16–.30 | .26–.50 | .56–1.13 | .52–.95 |
| Range | 0.01–0.04 | 0.16–0.35 | 0.25–0.51 | 0.49–1.19 | 0.46–0.91 |
| CL/F, mL/h | 11 011 (44.7) | 5360 (26.8) | 6765 (26.7) | 4779 (27.9) | 7159 (18.4) |
| 95% CI | 7033–17 238 | 4064–7070 | 5139–8905 | 3587–6367 | 5914–8667 |
| Range | 7519–24 568 | 3487–6941 | 4795–8933 | 3713–7881 | 5749–8981 |
| Accumulation ratio | |||||
| AUC0-τ | 1.54 (24.5) | 2.29 (11.2) | 1.93 (18.6) | 2.09 (37.5) | 2.25 (72.1) |
| 95% CI | 1.14–2.07 | 2.04–2.58 | 1.59–2.34 | 1.38–2.96 | 1.14–4.44 |
| Range | 1.09–1.95 | 2.05–2.69 | 1.49–2.59 | 1.31–2.73 | 1.50–8.27 |
| Cmax | 0.93 (171.7) | 2.03 (24.4) | 1.73 (17.6) | 2.02 (37.5) | 1.98 (69.4) |
| 95% CI | .27–3.18 | 1.57–2.61 | 1.47–2.07 | 1.38–2.96 | 1.03–3.82 |
| Range | 0.09–1.86 | 1.52–2.91 | 1.45–2.29 | 1.17–3.25 | 1.34–6.93 |
| Cτ | 1.48 (22.2) | 2.30 (6.4) | 1.94 (20.8) | 1.90 (16.0) | 1.98 (61.2) |
| 95% CI | 1.17–1.86 | 2.15–2.46 | 1.56–2.41 | 1.61–2.24 | 1.10–3.58 |
| Range | 1.09–2.07 | 2.08–2.46 | 1.48–2.55 | 1.44–2.26 | 1.35–6.09 |
Abbreviations: AUC0-24, area under the concentration-time curve from 0 to 24 hours; AUC0-τ, area under the concentration-time curve from time 0 to the end of the dosing interval; CI, confidence interval; CL/F, apparent oral clearance; Cmax, maximum observed concentration; Cτ, concentration at the end of the dosing interval; CVb, between-participant coefficient of variation; GSK’254, GSK3640254; HIV-1, human immunodeficiency virus type 1; PK, pharmacokinetic; tmax, time to Cmax.
Except where noted for tmax.
One participant was excluded from PK analysis on day 1 due to vomiting postdose ≤1 × tmax.