TABLE 5.
Summary of PK parameters of multiple dose study (MAD).
| Variable (unit) | 50 mg (N = 12) | 150 mg (N = 9) | |||
|---|---|---|---|---|---|
| Day 1 | Day 28 | Day 1 | Day 28 | ||
| Tmax (h)* | Median (Range) | 1.38 (0.25–4.00) | 1.13 (0.25–3.00) | 1.50 (0.50–3.00) | 1.00 (0.75–1.50) |
| C max (ng/ml) | Mean ± SD | 869.32 ± 350.29 | 1,048.58 ± 381.02 | 2,583.06 ± 790.49 | 3,311.59 ± 699.20 |
| GM (95%CI) | 800.27 (646.76, 1,091.88) | 992.82 (806.50, 1,290.66) | 2,462.57 (1975.44, 3,190.68) | 3,244.59 (2,774.14, 3,849.04) | |
| AUClast (ng.h/ml) | Mean ± SD | 3,388.92 ± 884.45a | 6,288.65 ± 1955.92 | 9,644.49 ± 2,730.91a | 14,217.39 ± 2,524.40 |
| GM (95%CI) | 3,292.26 (2,826.98, 3,950.87) | 5,996.61 (5,045.94, 7,531.37) | 9,319.60 (7,545.33, 11,743.7) | 14,034.9 (12,277.0, 16,157.8) | |
| AUC0-inf (ng.h/ml) | Mean ± SD | 3,683.53 ± 936.03a | 6,463.85 ± 1961.86 | 10,413.09 ± 3,037.68a | 14,410.00 ± 2,568.95 |
| GM (95%CI) | 3,582.61 (3,088.82, 4,278.25) | 6,178.82 (5,217.36, 7,710.34) | 10,047.6 (8,078.13, 12,748.1) | 14,223.90 (12,435.30, 16,384.70) | |
| AUC 0–24 (h·ng/ml) | Mean ± SD | 3,388.92 ± 884.45 | 5,307.37 ± 1,474.97 | 9,644.49 ± 2,730.91 | 12,088.55 ± 2,265.08 |
| GM (95%CI) | 3,292.26 (2,826.98, 3,950.87) | 5,105.96 (4,370.24, 6,244.51) | 9,319.60 (7,545.33, 11,743.7) | 11,915.6 (10,347.5, 13,829.6) | |
| AUC 0–48 (h·ng/ml) | Mean ± SD | - | 6,089.80 ± 1727.59 | - | 13,594.22 ± 2,406.65 |
| GM (95%CI) | - | 5,853.08 (4,992.16, 7,187.44) | - | 13,420.8 (11,744.3, 15,444.1) | |
| AUC 0–96 (h·ng/ml) | Mean ± SD | - | 6,382.18 ± 1901.64 | - | 14,249.44 ± 2,502.39 |
| GM (95%CI) | - | 6,110.85 (5,173.95, 7,590.42) | 14,070.6 (12,325.9, 16,172.9) | ||
| Kel (1/h) (0–24 h) | Mean ± SD | 0.10 ± 0.02 | 0.11 ± 0.01 | 0.10 ± 0.02 | 0.11 ± 0.02 |
| GM (90%CI) | 0.10 (0.09, 0.12) | 0.11 (0.10, 0.12) | 0.10 (0.09, 0.11) | 0.10 (0.09, 0.12) | |
| Kel (1/h) (0–96 h) | Mean ± SD | - | 0.06 ± 0.02 | - | 0.04 ± 0.01 |
| GM (95%CI) | - | 0.05 (0.04, 0.07) | - | 0.04 (0.03, 0.05) | |
| T1/2 (h) (0–96 h)* | Mean ± SD | - | 14.063 ± 4.49 | - | 17.629 ± 4.13 |
| GM (95%CI) | - | 13.31 (11.05, 17.08) | - | 17.23 (14.46, 20.80) | |
| Accumulation Ratio [AUC0-12] | Mean ± SD | 1.54 ± 0.27 | 1.27 ± 0.17 | ||
| GM (95%CI) | 1.57 (1.42, 1.75) | 1.27 (1.14, 1.41) | |||
| Accumulation Ratio [AUC0-24] | Mean ± SD | 1.57 ± 0.27 | 1.29 ± 0.18 | ||
| GM (95%CI) | 1.60 (1.46, 1.77) | 1.28 (1.15, 1.43) | |||
a
For day 1, AUClast and AUC0-inf from 0 to 24 plasma concentration-time profile.
GM: Geometric mean. 95% CI: 95% confidence interval.