Table 6.
Pharmacokinetic analysis of drug regimens in mice with reference to human studies
| Drug | Species | Dose | Route | Schedule | PK data at |
Analyte | AUClast (ng•hr/mL) |
Cmax (ng/mL) |
tmax (h) |
Terminal t1/2 (h) |
Cmin (ng/mL) |
Reference |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sirolimus | Mouse | 0.5 mg/kg | IP | q48h | 48h | Sirolimus | 4,276 ± 329 | 983 ± 98 | 1 | 13.6 | 14.9 ± 2.0 | |
|
| ||||||||||||
| Temsirolimus | Human | 25 mg | IV | qwk | D7 or D28 | Temsirolimus | 1,580 ± 270 | 595 ± 102 | 0.5 | 12.8 | Atkins et al., 2004 * | |
| Sirolimus | 3,810 ± 2,210 | 66 ± 35 | 1 | 48.8 | ||||||||
| Sum | 5,860 ± 2,340 | |||||||||||
|
| ||||||||||||
| Everolimus | Human | 10 mg | PO | qd | Everolimus | 514 ± 231 | 61 ± 17 | 13.2 ± 7.2 | Awada et al., 2008 * | |||
|
| ||||||||||||
|
Sunitinib
Malate |
Mouse | 10 mg/kg | G | q12h | 12h (D1) | Sunitinib | 449.8 ± 41.1 | 108.5 ± 5.5 | 2 | 2 | 4.2 ± 0.1 | |
|
Desethyl
Sunitinib |
174.4 ± 24.0 | 37.8 ± 0.2 | 2 | 2.6 | 3.0 ± 0.1 | |||||||
| Sum | 624.2 | 7.2 | ||||||||||
|
| ||||||||||||
| Sunitinib Malate |
Human | 50 mg | PO | qd (D1-28) | 24h (D1) | Sunitinib | 420 + 210 | 27.7 ± 14.1 | 5 | Faivre et al., 2006* | ||
| Desethyl Sunitinib | 63.6 ± 33.7 | 4.1 ± 2.2 | 5 | |||||||||
| Sum | 483.6 | |||||||||||
|
| ||||||||||||
| Sunitinib Malate |
Human | 50 mg | PO | qd (D1-28) | 24h (D28) | Sunitinib | 1,296 ± 609 | 72.2 ± 31.0 | 8.5 | 44.0 ± 26.0 | Faivre et al., 2006* | |
| Desethyl Sunitinib | 592 ± 391 | 33.7 ± 24.6 | 6.5 | 18.8 ± 8.5 | ||||||||
| Sum | 1,888 | 62.8 | ||||||||||
|
| ||||||||||||
| Erlotinib | Mouse | 12.5 mg/kg | G | q12h | 12h (D1) | Erlotinib | 27,042 ± 2,569 | 3,513 ± 271 | 3 | 3.1 | 521 ± 169 | |
|
Desmethyl
erlotinib |
3,970 ± 330 | 526 ± 77 | 3 | 2.5 | 50 ± 23 | |||||||
|
| ||||||||||||
| Erlotinib | Human | 150 mg | PO | qd | 24h (D1) | Erlotinib | 11,860 ± 5,010 | 872 ± 399 | 3 | 385 ± 213 | Raizer et al., 2010 * | |
| Desmethyl erlotinib |
835 ± 479 | 68 ± 45 | 3.6 | 25 ± 18 | ||||||||
|
| ||||||||||||
| Erlotinib | Human | 150 mg | PO | qd | 24h (D28) | Erlotinib | 43,760 ± 22,560 | 2,528 ± 1,187 | 24.2 | 1,473 ± 877 |
Tan et al., 2004 * | |
|
| ||||||||||||
| Dovitinib | Mouse | 30 mg/kg | G | qd | 24h (D1) | Dovitinib | 6078 ± 710 | 373 ± 14.6 | 6 | 5.4 | 41.2 ± 9.3 | |
| Dovitinib | Human | 500 mg | PO | 5 d on/2 d off |
24h (D1) | Dovitinib | 2200-8251 | 180-487 | Angevin, et al 2009 | |||
|
| ||||||||||||
| Dovitinib | Human | 500 mg | PO | qd | 24h (D1) | Dovitinib | 3734 ± 2115 | 223 ± 128 | Kim, et al 2011* | |||
| (D15) | Dovitinib | 4340 ± 3775 | 267 ± 178 | 21 | ||||||||
Pharmacokinetic parameters (mean ± SE) based on noncompartmental analysis using WinNonlin (Pharsight Corp.).
*
Mean ± SD; IP, intraperitoneal; IV, intravenous; PO, orally; G, gavage; qwk, weekly; qd, daily.