TABLE 3.
Pharmacokinetic parameters of conjugates 2, 3, 4, 5 and 6 and release of their respective payloads.
| Parameter | Compound | ||||
|---|---|---|---|---|---|
| 2 | 3 | 4 | 5 | 6 | |
| CLp (mL/min/kg) | 2.33 ± 0.44 | 6.60 ± 0.95 | 1.47 ± 0.06 | 5.50 ± 2.35 | 1.69 ± 0.15 |
| Vss (L/kg) | 0.627 ± 0.344 | 0.0366 ± 0.0053 | 0.157 ± 0.015 | 0.600 ± 0.515 | 0.0377 ± 0.0050 |
| t1/2 (h) | 8.31 ± 5.49 | 0.240 ± 0.050 | 2.30 ± 0.95 | 4.88 ± 4.37 | 0.442 ± 0.023 |
| AUC0-inf (µmol*hr/L) | 2.52 ± 0.61 | 0.801 ± 0.126 | 3.03 ± 0.11 | 1.09 ± 0.49 | 2.98 ± 0.25 |
| payload/parent AUC ratio | 0.0105 | 0.307 | NC | NC | NC |
AUC, area under the plasma concentration-time profile; AUC0-inf, area under the plasma concentration-time profile from time 0 to infinity; Clp, plasma clearance; t1/2, elimination half-life; Vss, volume of distribution at steady-state; NC, not calculated as warhead not detected (LLOQ < 0.0005 µM).