TABLE 1.
Pharmacokinetic parameters by cohort for BAL4815 estimated after once-daily oral administrations of BAL8557a
| Cohortb and study day | Tmax (h) | Cmax (μg/ml) | AUC0-24 h (μg · h/ml) | AUC0-∞ (μg · h/ml)c | t1/2 (h) | VSS/F (liters) | CLSS/F (liters/h) |
|---|---|---|---|---|---|---|---|
| Cohort 1 | |||||||
| Day 1 | 2.0 (2.0-3.0) | 1.10 (±0.173) | 8.75 (±1.26) | — | — | — | — |
| Day 8 | 2.0 (1.5-3.0) | 1.20 (±0.215) | 18.1 (±4.45) | — | — | — | — |
| Day 14 | 3.0 (1.25-4.0) | 1.40 (±0.178) | 22.1 (±4.92) | — | — | — | 2.36 (±0.479) |
| Day 21 | 2.25 (1.5-3.0) | 1.37 (±0.230) | 21.6 (±4.30) | 130 (±26.5) | 98.4 (±21.3) | 346 (±112) | 2.39 (±0.430) |
| Cohort 2 | |||||||
| Day 1 | 2.0 (1.25-3.07) | 1.85 (±0.326) | 18.5 (±3.11) | — | — | — | — |
| Day 8 | 3.0 (2.0-12.0) | 2.33 (±0.472) | 34.0 (±5.70) | — | — | — | — |
| Day 14 | 2.25 (1.5-4.0) | 2.61 (±0.365) | 41.5 (±6.02) | — | — | — | 2.45 (±0.356) |
| Day 21 | 3.5 (2.0-4.0) | 2.56 (±0.434) | 40.3 (±4.28) | 255 (±80.5) | 84.5 (±28.3) | 308 (±118) | 2.51 (±0.275) |
a
Values are presented as arithmetic means plus or minus SD for six subjects; median and range are presented for Tmax.
b
For cohort 1, loading doses of 100-mg equivalents of BAL4815 were followed by once-daily maintenance doses of 50-mg equivalents of BAL4815; for cohort 2, loading doses of 200-mg equivalents of BAL4815 were followed by once-daily maintenance doses of 100-mg equivalents of BAL4815.
c
—, values could not be reliably estimated as plasma samples could be collected during only a 24-h interval.