TABLE 3.
ADC pharmacokinetics demonstrate delayed clearance and degradation of conjugatesa
| Compound | PK summary novel ADCs |
||||||||
|---|---|---|---|---|---|---|---|---|---|
| AB 482 MIC (μg/ml) | AB 317 MIC (μg/ml) | Cmax (SD) | T1/2 (h) (SD) | AUC0–24 (μg · h/ml) (SD) | 2-h TM/EM (%) (SD) | 24-h TM/EM (%) (SD) | 24-h AUC/MIC AB 482 | 24-h AUC/MIC AB 317 | |
| CTC-171 | 8 | 8 | 5.8 (2.1) | 9.9 | 97.0 (23.4) | 22.8 (15.0) | 3.7 (1.3) | 12.1 | 12.1 |
| CTC-172 | 16 | 16 | 5.6 (1.4) | 21.5 | 49.2 (4.2) | 18.2 (0.9) | 5.4 (1.0) | 3.1 | 3.1 |
| CTC-173 | 16 | 8 | 7.3 (0.9) | 22.1 | 90.6 (9.6) | 50.6 (9.4) | 18.2 (3.3) | 5.7 | 11.3 |
| CTC-174 | 16 | 16 | 13.3 (3.2) | 21.7 | 141.0 (9.7) | 39.4 (9.5) | 17.0 (1.6) | 8.8 | 8.8 |
a
Naive neutropenic mice were administered the 20 mg/kg of the indicated ADC. Whole blood was isolated and LPS ELISA was used to calculate the Cmax, T1/2, and AUC0–24. The percentage of TM-EM conjugate relative to total EM calculated at 2 and 24 h postinjection indicates the percentage of intact ADC at the indicated time.