Pharmacokinetic parameters in mice for the antibody drug conjugate huC242-DM1, its antibody component huC242, and the stable mertansine analog, maytansine (May)
Test Article (Compartment) | Measured Entity | Dose (D) per Kilogram | t1/2(β) | kβ (Period) | AUCtot | CL | VSS | Cmax | ||
|---|---|---|---|---|---|---|---|---|---|---|
| Protein | Linked DM1 | |||||||||
| mg kg −1 | h | h −1 | h mg ml −1 | ml h −1 kg −1 | ml kg −1 | μg ml−1 | ||||
| [125I]-huC242-DM1 (blood) | [125I] | 4.16 | 0.08 | 153.7 | 4.5 × 10−3 (10−168 h) | 8.18 | 0.51 | 115.7 | 74.8 | |
| [125I]-huC242 (blood) | [125I] | 4.16 | 155.8 | 4.45 × 10−3 (10−168 h) | 7.18 | 0.58 | 126.2 | 69.1 | ||
| huC242-DM1 (plasma) | huC242-DM1 | 10.0 | 0.16 | 42.2 | 1.64 × 10−2 (8−192 h) | 7.01 | 1.43 | 82.7 | 220.4 | |
| huC242 | 122.6 | 5.7 × 10−3 (8−192 h) | 27.68 | 0.36 | 66.8 | 248.5 | ||||
| huC242-[3H]-DM1 (serum) | [3H] | 3.93 | 0.06 | 23.9 | 2.9 × 10−2 (6-72 h) | 1.095 | 3.59 | 146.1 | 74.5 | |
| huC242 | 99.8 | 6.9 × 10−3 (6−72 h) | 6.41 | 0.61 | 88.9 | 86.6 | ||||
| May | ||||||||||
| Plasma | May | N/A | 0.1 | 2.1 | 0.34 | 110 | 3282 | 9800 | 0.4 | |
| Blood | 2.2 | 0.31 | 315 | 1068 | 3300 | 0.4 | ||||
| Blood cells |
|
|
| 2.1 | 0.31 | 596 | 630 | 1900 | 0.4 | |