Table 3.
Pharmacokinetic data of macromolecular constructs with covalent attachment of camptothecin derivatives.
| Compound (Drug) | Structure | MW (kDa) | wt% CPT | Subject (Sex) | Tumor Type | Route (time) | Dosing Schedule | Dose (mg/kg) | MTD (mg/kg) | t1/2 (h) | Plasma AUC (μg• h/mL) | Ref. |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NK012 (SN-38) | Micelle | 19 | 20 | Balb/c mice (F) | HT-29 (colon) | i.v. | q4d x 3 | 6 | 6 | 31 | 5000 | 259 |
| PEG(CPT)2 (CPT) | Linear Polymer | 40 | 2 | CD1 mice (F) | None | i.v. | q1d x 1 | 6 | NR | α: 0.1 β: 4 |
18300 | 267 |
| PEG(GlyCPT)2 (CPT) | Linear Polymer | 40 | 2 | CD1 mice (F) | None | i.v. | q1d x 1 | 17.5 | NR | α: 0.1 β: 10 |
53300 | 268 |
| Pegamotecan (CPT) | Linear Polymer | 40 | 2 | Adult humans | Solid | i.v. (1h) | q1d x 1, q3w | 3.8 | 3.8 | 94 | 29 | 269 |
| Pegamotecan (CPT) | Linear Polymer | 40 | 2 | Adult humans | Solid + Lymphoma | i.v. (1h) | q1d x 1, q3w | 1.75 | 1.75 | 44 | 27 | 270 |
| IT-101 (CPT) | Linear Polymer | 85 | 5 | SD rats | None | i.v. | q1d x 1 | 1 | 8.8 | α: 0.4 β: 6 γ: 20 |
700 | 273 |
| PLGA (CPT) | Linear Polymer | 33 | 38 | Athymic mice (F) | HT29 (colon) | i.v. | q1d x 1 | 18 | NR | 97 | 240 | 279 |
| PLGA (CPT) | Linear Polymer | Adult humans | Solid | i.v. | q1d x 1, q1w | 25 | 25 | 63 | 27 | 280 | ||
| HPMA (CPT) | Linear Polymer | 28 | 5 | Balb/c mice (M) | None | i.v. | q1d x 1 | 20 | NR | 27 | 1121 | 281 |
| HPMA (CPT) | Linear Polymer | 21 | 10 | Balb/c mice (M) | None | i.v. | q1d x 1 | 20 | NR | 20 | 500 | 281 |
| HPMA (CPT) | Linear Polymer | 20 | 10 | Adult Humans | Solid | i.v. | q1d x 3 | 68 | 68 | 8 | 8700 | 283 |
| T-0128 (SN-38) | Linear Polymer | 130 | 5 | Wistar rats (F) | Walker 256 (sarcoma) | i.v. | q1d x 1 | 1 | 100 | α: 4 β: 17 | 101 | 288 |
| T-0128 (SN-38) | Linear Polymer | 130 | 5 | Balb/c mice (M) | St-4 (gastric) | i.v. | q1d x 1 | 40 | 80 | 30 | 23900 | 292 |
| DE-310 (DX-8951) | Linear Polymer | 300 | 8 | Mice | Meth A (sarcoma) | i.v. | q1d x 1 | 5.7 | 5.7 | NR | 6300 | 293 |
| DE-310 (DX-8951) | Linear Polymer | 300 | 8 | Adult humans | Solid | i.v. (3h) | q1d x 1, q6w | 0.016 | 0.016 | 418 | 1180 | 298 |
| PEG-PLL (CPT) | Branched Polymer | 40 | 6 | Balb/c mice (F) | C26 (colon) | i.v. | q1d x 1 | 10 | NR | 31 | 1400 | 303 |
| DTS-108 (SN-38) | Peptide targeted | 3.6 | 11 | Beagle dogs | None | i.v. (0.8 h) | q1d x 1 | 2.2 | 2.2 | NR | 4.8 | 310 |
Abbreviations: PLGA, poly(L-glutamic acid MTD, maximum tolerated dose; AUC, area under the curve; CPT, camptothecin; TPT, topotecan; CPT-11, irinotecan; GG211, lurtotecan; DX-8951, exatecan; M, male; F, female; SD, Sprague-Dawley; i.v., intravenous; NR, not reported.
Dosing abbreviations: q4d x 3, one dose every four days for three total doses; q1d x 1, one dose; q1d x 1, q3w, once a week every three weeks; q1d x 1, q6w, once a week every six weeks.