Pharmacokinetic parameters of the major metabolite M23 in human plasma
Blood samples were collected at selected time intervals from each subject. Plasma samples were prepared by centrifugation. Total radioactivity in plasma was determined by scintillation counting. After extraction, plasma samples were quantified for KAE609 and M23 by LC-MS/MS analysis. PK parameters were calculated using Phoenix (WinNonlin, version 6.2).
| Subject ID | tmax | Cmax | AUC0–24 h | AUClast | AUCinf | t1/2 | CL/F | Vz/F |
|---|---|---|---|---|---|---|---|---|
| h | ng/ml | μg⋅h/ml | h | l/h | liters | |||
| 5101 | 24.0 | 390 | 6.37 | 27.0 | 27.1 | 36.0 | 11.1 | 575 |
| 5102 | 24.0 | 90.1 | 1.64 | 8.34 | 8.42 | 43.0 | 35.6 | 2208 |
| 5103 | 8.00 | 282 | 5.51 | 22.0 | 22.0 | 28.2 | 13.6 | 554 |
| 5104 | 24.0 | 336 | 6.49 | 21.9 | 21.9 | 32.0 | 13.7 | 631 |
| 5105 | 24.0 | 75.9 | 1.56 | 6.68 | 6.76 | 38.2 | 44.4 | 2447 |
| 5106 | 24.0 | 415 | 7.44 | 23.5 | 23.7 | 34.3 | 12.7 | 626 |
| Mean | NA | 265 | 4.83 | 18.2 | 18.3 | 35.3 | 21.9 | 1174 |
| SD | NA | 148 | 2.58 | 8.52 | 8.54 | 5.09 | 14.4 | 898 |
| %CV mean | NA | 56.0 | 53.4 | 46.8 | 46.6 | 14.4 | 65.7 | 76.5 |
| Geomean | NA | 217 | 4.04 | 16.0 | 16.1 | 35.0 | 18.6 | 938 |
| %CV geomean | NA | 89 | 83.00 | 66.0 | 65.5 | 14.6 | 65.4 | 80.3 |
| Median | 24.0 | 309 | 5.94 | 22.0 | 22.0 | 35.1 | 13.6 | 629 |
| Minimum | 8.00 | 75.9 | 1.56 | 6.68 | 6.76 | 28.2 | 11.1 | 554 |
| Maximum | 24.0 | 415 | 7.44 | 27.0 | 27.1 | 43.0 | 44.4 | 2447 |
NA, not applicable (only the median and range are presented for tmax).