Table 7.
Pharmacokinetic parameters of ABT-288 (mean ± SD) after administration of escalating multiple once-daily doses of ABT-288 to healthy young adults and elderly subjects
| Parameter | Healthy young adults | Elderly subjects | |||||
|---|---|---|---|---|---|---|---|
| 0.5 mg (n = 9) | 1.5 mg (n = 9) | 3 mg (n = 9) | 0.5 mg (n = 6) | 1.5 mg (n = 6) | 3 mg (n = 6) | 5 mg (n = 3) | |
| Day 14 | Day 12 | ||||||
| Cmax (ng ml−1) | 0.85 ± 0.24 | 2.56 ± 0.451 | 5.14 ± 1.25 | 0.48 ± 0.13 | 2.32 ± 0.23 | 4.62 ± 1.43 | 6.86 ± 1.55 |
| tmax (h) | 6 (2–6) | 3 (3–6) | 6 (2–6) | 3 (1.5–9) | 3.5 (3–6) | 4 (2–9) | 4 (3–12) |
| Cmin (ng ml−1) | 0.44 ± 0.15 | 1.33 ± 0.23 | 2.48 ± 0.67 | 0.27 ± 0.08 | 1.37 ± 0.17 | 2.71 ± 1.11 | 3.47 ± 0.40 |
| t1/2* (h) | 40 ± 10 | 45 ± 7.5 | 49 ± 11 | 50 ± 20 | 52 ± 8.3 | 53 ± 17 | 53 ± 13 |
| AUC(0,24 h) (ng h ml−1) | 15 ± 4.0 | 46 ± 7.6 | 92 ± 24 | 8.5 ± 2.3 | 43 ± 4.9 | 87 ± 27 | 120 ± 20 |
| CL/F (l h−1) | 36 ± 8.5 | 34 ± 6.4 | 35 ± 13 | 64 ± 26 | 35 ± 4.1 | 38 ± 15 | 42 ± 6.7 |
| Rac† | 3.6 (2.6–4.1) | 3.7 (2.7–4.5) | 3.4 (2.6–4.1) | 3.7 (2.7–7.3) | 4.2 (3.2–4.9) | 4.1 (2.4–4.7) | 4.2 (3.8–4.6) |
*
Harmonic mean ± pseudo-standard deviation; half-life from the plasma concentrations during the terminal phase after administration of the last dose.
†
Observed accumulation ratio (calculated as the ratio of AUC(0,24 h) on day 14 or 12 to AUC(0,24 h) on day 1), median and range are presented. ND, Not determined.