Table 4.
Pharmacokinetic results
| Regimen | Analyte | ABT-751 dose (mg) | Cycle 1 Day 1 |
Cmax (μg/ml) | AUC0–8 (μg*h/ml) | Tmax (h) | CL (L/h) | Cycle 1 Day 15 |
Ctrough (μg/ml) |
|---|---|---|---|---|---|---|---|---|---|
| N | N | ||||||||
| QD | ABT-751 | 150 | 2 | 5.99±3.65 | 17.68±1.61 | 1.3±1.1 | 8.52±0.77 | 2 | 0.84±0.51 |
| 200 | 23 | 9.06±4.54 | 32.00±10.97 | 2.0±1.3 | 7.25±3.59 | 19 | 0.54±0.45 | ||
| 250 | 3 | 10.92±3.34 | 45.54±10.46 | 1.3±0.6 | 5.70±1.40 | NA | – | ||
| BID | ABT-751 | 25 | 1 | 2.03 | 5.54 | 0.75 | 4.51 | 1 | 0.26 |
| 50 | 2 | 4.23±1.00 | 13.19±2.13 | 0.8±0.3 | 3.84±0.62 | 1 | 0.48 | ||
| 100 | 10 | 5.60±2.18 | 18.47±4.96 | 2.5±2.6 | 6.05±2.80 | 8 | 1.09±0.60 | ||
| 125 | 6 | 4.98±1.96 | 19.80±5.14 | 1.7±0.5 | 6.76±2.14 | 6 | 1.16±0.77 | ||
| QD | ABT-751G | 150 | 2 | 2.64±0.17 | 15.45±0.86 | 4.0±0.0 | 9.72±0.54 | 2 | 2.56±1.34 |
| 200 | 23 | 4.55±1.68 | 25.70±11.10 | 4.5±2.2 | 9.56±5.4 | 19 | 2.07±1.28 | ||
| 250 | 3 | 4.47±1.28 | 27.65±9.30 | 3.3±2.3 | 9.66±2.78 | NA | – | ||
| BID | ABT-751G | 25 | 1 | 0.65 | 4.24 | 4.0 | 5.89 | 1 | 1.00 |
| 50 | 2 | 1.44±0.49 | 8.44±2.89 | 5.0±1.4 | 6.29±2.16 | 1 | 3.28 | ||
| 100 | 10 | 3.28±2.48 | 18.28±15.02 | 4.7±2.3 | 8.05±4.56 | 8 | 7.23±11.10 | ||
| 125 | 6 | 3.18±1.56 | 17.28±8.31 | 4.7±2.4 | 8.99±5.23 | 6 | 3.65±1.47 | ||
| QD | ABT-751S | 150 | 2 | 4.16±1.22 | 25.16±10.13 | 4.0±0.0 | 6.49±2.61 | 2 | 3.24±2.75 |
| 200 | 23 | 7.37±3.16 | 38.12±16.08 | 4.0±2.4 | 6.56±4.80 | 19 | 2.07±1.24 | ||
| 250 | 3 | 8.18±3.53 | 39.01±12.80 | 3.0±2.6 | 6.94±2.48 | NA | – | ||
| BID | ABT-751S | 25 | 1 | 0.85 | 5.87 | 4.0 | 4.26 | 1 | 1.40 |
| 50 | 2 | 1.80±0.00 | 11.09±0.33 | 4.0±2.8 | 4.51±0.14 | 1 | 1.70 | ||
| 100 | 10 | 3.44±1.53 | 20.03±11.47 | 4.6±2.1 | 8.16±8.63 | 8 | 5.31±5.73 | ||
| 125 | 6 | 4.52±2.27 | 23.70 ± 9.67 | 3.7±2.0 | 6.28±3.22 | 6 | 4.18±1.73 | ||
| QD | ABT-751G/ABT-751 | 150 | 2 | – | 0.88±0.03 | – | – | – | – |
| 200 | 23 | – | 0.83±0.31 | – | – | – | – | ||
| 250 | 3 | – | 0.60±0.10 | – | – | – | – | ||
| BID | – | 25 | 1 | – | 0.77 | – | – | – | – |
| 50 | 2 | – | 0.63±0.12 | – | – | – | – | ||
| 100 | 10 | – | 1.00±0.77 | – | – | – | – | ||
| 125 | 6 | – | 0.85±0.29 | – | – | – | – | ||
| QD | ABT-751S/ABT-751 | 150 | 2 | – | 1.40±0.45 | – | – | – | – |
| 200 | 23 | – | 1.33±0.85 | – | – | – | – | ||
| 250 | 3 | – | 0.84±0.09 | – | – | – | – | ||
| BID | – | 25 | 1 | – | 1.06 | – | – | – | – |
| 50 | 2 | – | 0.85±0.11 | – | – | – | – | ||
| 100 | 10 | – | 1.13±0.56 | – | – | – | – | ||
| 125 | 6 | – | 1.21±0.47 | – | – | – | – |
Data are expressed as mean±SD.
ABT-751G, ABT-751 glucuronide; ABT-751S, ABT-751 sulfate; AUC0–8, partial area under the plasma concentration–time curve from time 0 to 8 h; BID, twice daily; CL, clearance; Cmax, maximum observed plasma concentration; Ctrough, plasma predose concentration at day 15; NA, not available; QD, once daily; Tmax, time to Cmax.