Rituximab (IDEC-C2B8): Validation of a sensitive enzyme-linked immunoassayapplied to a clinical pharmacokinetic study

Rituximab is a chimeric monoclonal antibody (MAb) directed against the B-ce ll CD20 antigen that has been approved for therapy of relapsed and resistan t follicular. non-Hodgkin's lymphoma (NHL). This study describes the develo pment and validation of a highly sensitive, rapid, accurate, precise enzyme -linked immunosorbent assay (ELISA) to measure Rituximab serum concentratio ns. This study also describes the application of the ELISA method to a phar macokinetic study in a homogeneous group of patients with follicular lympho ma who received 4 weekly doses of MAb at the standard dose of 375 mg/m(2) a s consolidation of chemotherapy. In the patients in this study, the median Rituximab serum concentrations increased during therapy, and showed a slow decline during the posttreatment period. The Rituximab elimination half-lif e of approximately 20 days accounts for the demonstrated accumulation of MA b in serum samples. Because previous pharmacokinetic studies showed a corre lation between Rituximab serum levels and tumor response, the ELISA method used in this study, which allows a precise control of serum concentrations, could be useful for predicting the final response to the MAb and for selec ting patients able to benefit from higher dosage or repeated drug administr ation.