Rituximab (IDEC-C2B8): validation of a sensitive enzyme-linked immunoassay applied to a clinical pharmacokinetic study.
Rituximab is a chimeric monoclonal antibody (MAb) directed against the B-cell CD20 antigen that has been approved for therapy of relapsed and resistant follicular non-Hodgkin's lymphoma (NHL). This study describes the development and validation of a highly sensitive, rapid, accurate, precise enzyme-linked immunosorbent assay (ELISA) to measure Rituximab serum concentrations. This study also describes the application of the ELISA method to a pharmacokinetic study in a homogeneous group of patients with follicular lymphoma who received 4 weekly doses of MAb at the standard dose of 375 mg/m2 as 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-life of approximately 20 days accounts for the demonstrated accumulation of MAb in serum samples. Because previous pharmacokinetic studies showed a correlation 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 selecting patients able to benefit from higher dosage or repeated drug administration.
Iacona
I
I
Department of Pharmacology, University of Pavia, IRCCS Policlinico San Matteo, Italy.
Lazzarino
M
M
Avanzini
M A
MA
Rupolo
M
M
Arcaini
L
L
Astori
C
C
Lunghi
F
F
Orlandi
E
E
Morra
E
E
Zagonel
V
V
Regazzi
M B
MB
D000911:Antibodies, Monoclonal / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001825:Body Fluid Compartments; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004355:Drug Stability; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D006801:Humans; D007262:Infusions, Intravenous; D008224:Lymphoma, Follicular / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism; D011241:Prednisone / Q000008:administration & dosage; D015203:Reproducibility of Results; D000069283:Rituximab; D012680:Sensitivity and Specificity; D014750:Vincristine / Q000008:administration & dosage
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone