A population pharmacokinetic-pharmacodynamic analysis of single doses of clenoliximab in patients with rheumatoid arthritis.

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Mould DR, Davis CB, Minthorn EA, Kwok DC, Elliott MJ, Luggen ME, Totoritis MC

A population pharmacokinetic-pharmacodynamic analysis of single doses of clenoliximab in patients with rheumatoid arthritis.

Clin Pharmacol Ther. 1999 Sep;66(3):246-57.

PubMed ID
10511060 [ View in PubMed
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Abstract

Clenoliximab (IDEC-151) is a macaque-human chimeric monoclonal antibody (immunoglobulin G4) specific for the CD4 molecule on the surface of T lymphocytes. It is being studied in patients with rheumatoid arthritis in which T cell activation orchestrates inflammation and tissue damage. In this initial study in humans, the pharmacokinetics and pharmacodynamics of clenoliximab were investigated after single intravenous infusion. Blood was collected up to 12 weeks after dose administration to measure clenoliximab concentration, CD4+ T-cell count, CD4 antigen coating, and CD4 cell surface density. Clenoliximab displayed nonlinear pharmacokinetic behavior and caused an 80% reduction in CD4 density for up to 3 weeks, without depleting T cells. A pharmacokinetic-pharmacodynamic model was developed that described the relationship between antibody concentration, antigen coating, and the observed decreases in CD4 cell surface density. This was used to anticipate the effects of clenoliximab in untested regimens and optimize the design of future clinical trials.

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