TABLE 4.
Summary of MK-8507 plasma pharmacokinetics following administration of multiple oral MK-8507 doses of a tablet (100 to 400 mg) administered once weekly for 3 weeks to adults without HIVc
| Dose (mg) | Wk | No. of patients | AUC0–168a (geometric mean [95% CI] [μM·h]) | Cmaxa (geometric mean [95% CI] [μM]) | C168hra (geometric mean [95% CI] [μM]) | Tmax (median [min, max] [h]) | Apparent terminal t½b (geometric mean [%GVC] [h]) |
|---|---|---|---|---|---|---|---|
| 100 | 1 | 6 | 157 (129–190) | 2.94 (2.29–3.77) | 0.32 (0.23–0.45) | 3.00 (1.00–12.00) | |
| 2 | 6 | 0.39 (0.28–0.54) | |||||
| 3 | 6 | 185 (153–225) | 3.29 (2.57–4.22) | 0.37 (0.27–0.51) | 3.03 (1.00–6.00) | 66.7 (16.8) | |
| GMR (accumulation ratio, wk 3/wk 1 [90% CI]) | 6 | 1.18 (1.12–1.25) | 1.12 (0.96–1.30) | 1.14 (0.87–1.50) | |||
| 200 | 1 | 5/6 | 285 (231–353) | 4.87 (3.80–6.24) | 0.59 (0.42–0.84) | 5.00 (2.01–8.00) | |
| 2 | 5 | 0.70 (0.49–1.00) | |||||
| 3 | 5 | 352 (285–434) | 5.61 (4.33–7.26) | 0.72 (0.51–1.02) | 4.01 (2.00–8.00) | 74.2 (38.1) | |
| GMR (accumulation ratio, wk 3/wk 1 [90% CI]) | 5/6 | 1.23 (1.16–1.31) | 1.15 (0.98–1.36) | 1.22 (0.90–1.65) | |||
| 400 | 1 | 6 | 563 (464–682) | 10.8 (8.44–13.9) | 1.23 (0.90–1.70) | 4.00 (2.00–4.00) | |
| 2 | 6 | 1.11 (0.80–1.53) | |||||
| 3 | 6 | 694 (572–841) | 11.5 (8.94–14.7) | 1.49 (1.08–2.06) | 4.00 (2.00–4.03) | 73.1 (20.1) | |
| GMR (accumulation ratio, wk 3/wk 1 [90% CI]) | 6 | 1.23 (1.16–1.31) | 1.06 (0.91–1.23) | 1.21 (0.92–1.59) |
a
Back-transformed LSM and CI from linear mixed-effects model performed on natural log-transformed values.
b
Geometric mean and percentage of geometric coefficient of variation reported for t½.
c
AUC, area under the concentration-time curve; C168hr, trough concentration; CI, confidence interval; Cmax, maximum concentration; CV, coefficient of variation; GCV, geometric coefficient of variation; GMR, geometric mean ratio; LSM, least-squares mean; max, maximum; min, minimum; t1/2, terminal half-life; Tmax, time to maximum concentration.