Table 3.
Pharmacokinetic parameters for pertuzumaba
| Study type | Species/strain | No./sex | Route | Doses (mg/kg) | CL (mL/day/kg) | V c (mL/kg) | V ss (mL/kg) | αHL (day) | βHL (day) |
|---|---|---|---|---|---|---|---|---|---|
| SD PK | Mouse/CD-1 | 144/M | IV | 3, 30, 90 | 5.6–9.2 | 45–58 | 102–148 | 0.1–0.3 | 11.4–15.7 |
| SD PK | Rat/SD | 18/M | IV | 3, 30, 90 | 7.2–10.1 | 27–44 | 91–121 | 0.2–0.4 | 8.9–9.2 |
| SD PK | Monkey/Cyno | 8/M, 8/F | IV | 15, 50, 150 | 5.0–5.2 | 31–37 | 68–73 | 0.3–0.9 | 9.9–10.4 |
| MD Tox | Monkey/Cyno | 14/M, 14/F | IV | 15, 50, 150 | 5.1–7.4 | 36–41 | 64–80 | 0.5–0.6 | 8.1–10.6 |
CL clearance, V c volume of distribution of the central compartment, V ss volume of distribution at steady state, αHL initial half-life, βHL terminal half-life, SD Single-dose, MD Multi-dose, PK Pharmacokinetic, Tox Toxicology, IV Intravenous
aPharmacokinetics were characterized using a two-compartment model for the serum concentration-time data of individual animals (WinNonlin Professional Version 3.1, Pharsight Corp., Mountain View, CA, USA) using the Gauss–Newton algorithm and a reiterative weighting scheme (1/Ŷ). Serum pertuzumab concentrations found in the less-than-reportable range of the assay (LTR; <0.25 μg/mL) were not used for pharmacokinetic analysis, or in the group summary calculations. Data are ranges of group means