Table 1.
MTD of SAPDs 2 to 4 by dose escalation studies in healthy athymic nude mice
| Prodrug | Dose, mg/kg | Maximum % BW loss, d | Survival/total |
| SAPD 2 | 108 | N.D. | 0/3 |
| 72 | 11.4 (2) | 2/3 | |
| 54 | 3.5 (2) | 3/3 | |
| 45 | 4.0 (2) | 3/3 | |
| 36 | 2.1 (6) | 3/3 | |
| 18 | 6.2 (5) | 3/3 | |
| SAPD 3 | 108 | N.D. | 2/3 |
| 72 | 0 | 3/3 | |
| 54 | 1.6 (1) | 3/3 | |
| 45 | 2.5 (4) | 3/3 | |
| 36 | 1.4 (4) | 3/3 | |
| 18 | 5.5 (4) | 3/3 | |
| SAPD 4 | 108 | N.D. | 1/3 |
| 72 | 1.2 (1) | 2/3 | |
| 54 | 3.9 (3) | 3/3 | |
| 45 | 0 | 3/3 | |
| 36 | 7.2 (2) | 3/3 | |
| 18 | 3.1 (5) | 3/3 |
A single i.v. injection of SAPDs was administered, and body weights (BWs) of mice were recorded for 2 wk (n = 3 for each group). All of the doses are CPT equivalent. The MTD of SAPD 1 was previously determined in our laboratory (SI Appendix, Table S1). SAPDs 1 to 4 have MTDs of 24, 54, 72, and 72 mg/kg, respectively. If the BW of a mouse decreases more than 20%, the mouse will be killed and counted as a death.