EFFICACY, PHARMACODYNAMICS, AND PHARMACOKINETICS OF CGP-51901, AN ANTIIMMUNOGLOBULIN-E CHIMERIC MONOCLONAL-ANTIBODY, IN PATIENTS WITH SEASONAL ALLERGIC RHINITIS

The efficacy, pharmacodynamics, and pharmacokinetics of CGP 51901, a r ecombinant monoclonal mouse-human chimeric anti-human immunoglobulin E (IgE) antibody were evaluated for 153 patients with seasonal allergic rhinitis treated with placebo or with 15, 30, or 60 mg CGP 51901 in s ix biweekly doses, Seasonal allergic rhinitis was chosen to validate t he concept of anti-IgE therapy because the causal and temporal relatio n between allergen confrontation and IgE-mediated evocation of symptom s is firmly established, A sustained 85% or greater reduction of serum free IgE levels was shown to be effective in improving clinical sympt oms, The concentration of CGP 51901 needed to maintain 85% or greater reduction of Ige was estimated to be about 5000 ng/ml, Baseline IgE le vels and body weights of the patients greatly influenced the pharmacok inetic and pharmacodynamic profiles of CGP 51901, A population model w as developed and refined to take into account patient baseline IgE lev el and body weight, The model was able to help predict multiple-dose p harmacokinetic and pharmacodynamic profiles on the basis of single-dos e pharmacokinetic and pharmacodynamic measurements in the therapeutica lly effective dose range.