PAGE. Abstracts of the Annual Meeting of the Population Approach Group in Europe.
PAGE 18 (2009) Abstr 1665 [www.page-meeting.org/?abstract=1665]
Poster: Applications- Biologicals/vaccines
E. Rouits, M. Lovern, M.L. Sargentini-Maier
UCB Pharma S.A.
Introduction: CDP791 is a Monoclonal antibody (Mab) showing non-linear pharmacokinetics. It is a VEGFR-2 (Vascular Endothelial Growth Factor Receptor-2) antagonist developed for use in cancer therapy.
Objectives: To develop a target-mediated drug disposition (TMDD) model to:
Methods: Data were available from a phase II study in patients with Stage IIIb or Stage IV non-squamous non-small cell lung cancer requiring chemotherapy. A Target-Mediated Drug Disposition (TMDD) model was implemented in NONMEM. It included a central and a peripheral compartment as well as a third compartment (binding compartment) linked to the central, to model drug/target binding. A linear clearance was defined from the central compartment as well as distribution parameters with the peripheral compartment. Elimination from the binding compartment was nonlinear and dependent on the prevalence of both the drug and the receptor.
Results: This TMDD model with two compartments (central and peripheral) and a third one for the drug/target binding described the PK adequately. The volume for the central compartment was around 3 L, which is closely similar to plasma volume. Linear clearance was 0.0101 L.h-1. Those values are consistent with pharmacokinetic parameters reported for other macromolecules presenting TMDD behavior. The target/drug binding was faster than both degradation and synthesis of the target, as is generally expected for the kinetics of such processes.
Conclusions: We have developed a specific TMDD model that describes adequately the PK of CDP791.