Pharmacokinetics of rituximab associated with CHOP chemotherapy in B-cell non-Hodgkin lymphoma.
The pharmacokinetics of rituximab administered alone at a dose of 375 mg/m(2) once a week have been widely studied but few data are available for the administration of rituximab in combination with other agents. We carried out a pilot pharmacokinetic study in 10 patients with B-cell non-Hodgkin lymphoma treated with rituximab associated with chemotherapy on a three-weekly basis. Patients received four courses of rituximab (375 mg/m(2)) associated with CHOP (cyclophosphamide, adriamycin, vincristine and prednisone) at 21-day intervals. Blood samples were collected from each patient at selected times throughout the treatment period and analysed using a validated enzyme-linked immunosorbent assay. The NONMEM software was used to obtain population and post hoc estimates of rituximab pharmacokinetic parameters and to study possible time-dependent variation during treatment. Pharmacokinetic parameters obtained from 10 patients were similar to those described for studies in the absence of chemotherapy. We did not observe any intra-subject variation in pharmacokinetic parameters over the treatment period. Our results suggest that rituximab pharmacokinetics is not affected by combination with CHOP chemotherapy. Nevertheless, the substantial intersubject variability observed in this small sample size highlights the need for further study of the determinants of rituximab pharmacokinetic variability.
Blasco
Hélène
H
Université François Rabelais de Tours; CHRU de Tours, laboratoire de pharmacologie et toxicology, 37044 Tours cedex, France.
Chatelut
Etienne
E
de Bretagne
Isabelle Benz
IB
Congy-Jolivet
Nicolas
N
Le Guellec
Chantal
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19 / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007262:Infusions, Intravenous; D018655:Lymphocyte Count; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D010865:Pilot Projects; D011241:Prednisone / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D000069283:Rituximab; D013997:Time Factors; D014750:Vincristine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D055815:Young Adult
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone