Table 1.
Pharmacokinetic properties and tissue distribution of Dox, DTS-201, and PhAc-ALGP-Dox and intermediates in E0771 tumor-bearing mice.
| Tumor-bearing mice (92 μmol/kg) | ||||||||
|---|---|---|---|---|---|---|---|---|
| Tissue | Drug | Metabolites | t max | C max | AUC | t 1/2α | t 1/2β | CL |
| Heart | PhAc-ALGP-Dox | PhAc-ALGP-Dox | 5 | 19 | 3.7 | 0.17 | — | — |
| GP-Dox | 5 | 1.65 | 2.3 | 0.3 | 7 | — | ||
| Dox | 30 | 4.12 | 94 | 8.2 | 28 | — | ||
| DoxOL | — | <LoQ | — | — | — | — | ||
| Doxorubicin | Dox | 30 | 115 | 1,933 | 5.6 | 34 | — | |
| DoxOL | 240 | 0.86 | 54 | 47 | — | — | ||
| DTS-201a | Succ-βALAL-Dox | 5 | 35.9 | 15.1 | 0.2 | 0.5 | — | |
| Dox | 60 | 10 | 266 | 8 | 39 | — | ||
| DoxOL | — | <LoQ | — | — | — | — | ||
| Kidney | PhAc-ALGP-Dox | PhAc-ALGP-Dox | 5 | 530 | 388 | 0.1 | 9 | — |
| LGP-Dox | 5 | 5.6 | 3.7 | 0.1 | 3.3 | — | ||
| GP-Dox | 5 | 54 | 288 | 0.2 | 12.7 | — | ||
| Dox | 5 | 80 | 584 | 1 | 16 | — | ||
| DoxOL | 30 | 1.96 | 20.8 | 1 | 19.7 | — | ||
| Doxorubicin | Dox | 30 | 339 | 6,025 | 2.7 | 36 | — | |
| DoxOL | 30 | 6.8 | 168 | 2.5 | 49 | — | ||
| DTS-201a | Succ-βALAL-Dox | 15 | 811 | 771 | 0.4 | 10.7 | — | |
| Dox | 240 | 93 | 1,983 | — | 17.6 | — | ||
| DoxOL | 240 | 1.48 | 49.7 | — | 27.1 | — | ||
| Liver | PhAc-ALGP-Dox | PhAc-ALGP-Dox | 5 | 69 | 152.5 | 0.7 | 16.8 | — |
| GP-Dox | 5 | 5.3 | 72.2 | 1.4 | 14.8 | — | ||
| Dox | 30 | 16 | 235 | 2.1 | 15 | — | ||
| DoxOL | 240 | 0.44 | 10.6 | — | 21.7 | — | ||
| Doxorubicin | Dox | 5 | 189 | 2,184 | 2.1 | 26 | — | |
| DoxOL | 1 | 6 | 104 | 2.2 | 33.3 | — | ||
| DTS-201a | Succ-βALAL-Dox | 15 | 49 | 48 | 0.6 | 20.5 | — | |
| Dox | 60 | 14 | 449 | 25.2 | — | — | ||
| DoxOL | 120 | 0.67 | 30.8 | — | 33.4 | — | ||
| Tumor | PhAc-ALGP-Dox | PhAc-ALGP-Dox | 5 | 25.2 | 16.9 | 0.3 | 2.6 | — |
| GP-Dox | 15 | 20.85 | 59.6 | 0.5 | 10 | — | ||
| Dox | 240 | 6.72 | 459 | — | 46 | — | ||
| DoxOL | — | <LoQ | — | — | — | — | ||
| Doxorubicin | Dox | 120 | 21.4 | 1,327 | — | 53 | — | |
| DoxOL | 2,880 | 0.12 | 8 | — | — | — | ||
| DTS-201a | Succ-βALAL-Dox | 5 | 56.5 | 25.6 | 0.4 | — | — | |
| Dox | 720 | 13.3 | 988 | — | 36 | — | ||
| DoxOL | — | <LoQ | — | — | — | — | ||
| Plasma | PhAc-ALGP-Dox | PhAc-ALGP-Dox | 5 | 560 | 156.5 | 0.21 | — | — |
| LGP-Dox | 5 | 0.74 | 0.133 | 0.15 | — | — | ||
| GP-Dox | 5 | 3.7 | 1.49 | 0.2 | — | — | ||
| Dox | 5 | 1.2 | 0.74 | 0.2 | 9 | — | ||
| DoxOL | — | <LoQ | — | — | — | — | ||
| Doxorubicin | Dox | 5 | 7.09 | 11.3 | 0.2 | 13 | 135 | |
| DoxOL | — | <LoQ | — | — | — | — | ||
| DTS-201a | Succ-βALAL-Dox | 5 | 243 | 1,21.3 | 0.25 | — | 12.6 | |
| Dox | 30 | 0.404 | 1.41 | 0.6 | 16.7 | — | ||
| DoxOL | — | <LoQ | — | — | — | — | ||
aFor DTS-201, only the parent molecule and Dox, but no intermediates, were measured.