Table 5.
Summary of MK-5108 plasma pharmacokinetic values following BID every 12-hours oral dosing in Cycle 1
| MK-5108 Dose | Panel | Dose # | AUC0-12h (μM*hr) | Cmax (μM) | C12h (μM) | Tmax* (hr) | t1/2 (hr) |
|---|---|---|---|---|---|---|---|
| 200 mg/day | 1 | Dose 1 | 17.5 ± 5.6 | 3.9 ± 0.7 | 0.35 ± 0.05 | 4 (2–4) | - |
| Dose 4 | 31.2 ± 16.3 | 4.8 ± 1.0 | 1.92 ± 1.91 | 4 (1–8) | 9.3 ± 1.2 | ||
| 400 mg/day | 1 | Dose 1 | 27.0 ± 12.2 | 6.7 ± 2.4 | 0.25 ± 0.13 | 2 (1–3) | - |
| Dose 4 | 75.7 ± 46.2 | 11.0 ± 5.3 | 2.02 ± 1.52 | 6 (3–6) | 8.7 ± 6.7 | ||
| 800 mg/day | 1 | Dose 1 | 69 ± 41.9 | 19.5 ± 5.5 | 1.68 ± 1.91 | 1 (0.5–4) | - |
| Dose 4 | 95.5 ± 44.9 | 20.0 ± 11.0 | 4.53 ± 2.68 | 1 (1–12) | 11.1 ± 1.1 | ||
| 1200 mg/day | 1 | Dose 1 | 96.6 ± 45.6 | 22.3 ± 12.7 | 2.12 ± 2.09 | 2 (2–3) | - |
| Dose 4 | 115.9 ± 61.4 | 25.0 ± 9.4 | 3.31 ± 0.53 | 3 (1–4) | 8.3 ± 3.3 | ||
| 1500 mg/day | 1 | Dose 1 | 83.2 ± 50.8 | 20.8 ± 10.6 | 1.04 ± 0.4 | 2 (1–3) | - |
| Dose 4 | 130.7 ± 53.2 | 28.9 ± 13.6 | 2.80 ± 1.26 | 2 (1–3) | 11.4 ± 2.0 | ||
| 1800 mg/day | 1 | Dose 1 | 100.8 ± 39.3 | 24.8 ± 9.6 | 4.78 ± 4.64 | 2 (2–3) | - |
| Dose 4 | 234.4 ± 62.7 | 50.2 ± 11.4 | 6.85 ± 3.96 | 3 (2–4) | 6.6 ± 0.6 | ||
| 100 mg/day | 2 | Dose 1 | 7.9 ± 2.0 | 2.3 ± 1.2 | 0.15 ± 0.12 | 2 (1–8) | - |
| Dose 4 | 10.8 ± 3.3 | 2.2 ± 1.0 | 0.21 ± 0.10 | 4 (1–8) | 13.5 ± 10.6 | ||
| 150 mg/day | 2 | Dose 1 | 15.0 ± 9.2 | 3.5 ± 2.0 | 0.33 ± 0.22 | 3.5 (2–4) | - |
| Dose 4 | 16.4 ± 8.9 | 3.2 ± 1.7 | 0.51 ± 0.37 | 5 (2–6) | 10.1 ± 5.0 | ||
| 225 mg/day | 2 | Dose 1 | 18.5 ± 6.2 | 5.0 ± 0.8 | 0.46 ± 0.26 | 2 (1–6) | - |
| Dose 4 | 23.4 ± 8.8 | 5.3 ± 1.7 | 0.66 ± 0.62 | 3 (2–8) | 9.2 ± 5.1 |
AUC0-12h = area under the plasma or serum concentration-time curve; Cmax = maximum concentration observed in plasma or serum; C12h = concentration at 12 hours post dose; hr = hour; SD = standard deviation; Tmax = time of occurrence of Cmax; t1/2 = apparent terminal half-life.
Median (range).