title: Population pharmacokinetics of Reditux™, a biosimilar Rituximab, in diffuse large B-cell lymphoma.
abstract: OBJECTIVE
  Rituximab (MabThera™, Roche) is a chimeric IgG1 monoclonal antibody targeting the CD20 surface antigen on normal and neoplastic B cells. It revolutionized the treatment of non-Hodgkin's lymphoma with superior progression-free and overall survival. However, its prohibitively high cost makes it inaccessible to majority of patients in developing countries. Reditux™ (Dr. Reddy's Laboratories, India), a biosimilar, was introduced in India in 2007 at nearly half the price of the innovator. However, there is a dearth of data regarding the pharmacokinetics and efficacy of Reditux™.
  
  
  METHODS
  Twenty-one patients of diffuse large B-cell lymphoma on R-CHOP regimen were enrolled for the study. Reditux™ was administered as a slow intravenous infusion at a dose of 375 mg/m(2) on day 1 of a 21-day cycle. Pharmacokinetic sampling was performed at pre-dose, post-infusion, 24, 48 h, 7 and 21 days. Rituximab levels were estimated by ELISA. Population pharmacokinetics was performed using NONMEM. In addition, B-cell count was determined at baseline and days 3 and 21 of the first cycle. Survival analysis was performed using Kaplan-Meier plots.
  
  
  RESULTS
  The volume of distribution of central compartment and clearance of Reditux™ were estimated at 0.95 L and 5.98 mL/h, respectively. No covariate effects were seen. B-cell count was completely depleted by day 3 and remained so on day 21. Overall survival was 84.6 % at a median follow-up of 36 months.
  
  
  CONCLUSIONS
  The pharmacokinetic profile and B-cell response to Reditux™ are comparable with those reported for MabThera™. Thus, MabThera™ can be substituted with Reditux™ for the treatment of B-cell lymphomas.
authors.affiliation: Department of Clinical Pharmacology, ACTREC, Tata Memorial Centre, Navi Mumbai, 410210, India. vgota76@gmail.com.
authors.forename: Vikram
authors.initials: V
authors.lastname: Gota
authors.affiliation: Department of Clinical Pharmacology, ACTREC, Tata Memorial Centre, Navi Mumbai, 410210, India.
authors.forename: Ashwin
authors.initials: A
authors.lastname: Karanam
authors.affiliation: Department of Clinical Pharmacology, ACTREC, Tata Memorial Centre, Navi Mumbai, 410210, India.
authors.forename: Sanhita
authors.initials: S
authors.lastname: Rath
authors.affiliation: Department of Clinical Pharmacology, ACTREC, Tata Memorial Centre, Navi Mumbai, 410210, India.
authors.forename: Akanksha
authors.initials: A
authors.lastname: Yadav
authors.affiliation: Department of Pathology, Tata Memorial Hospital, Mumbai, 400012, India.
authors.forename: Prashant
authors.initials: P
authors.lastname: Tembhare
authors.affiliation: Department of Pathology, Tata Memorial Hospital, Mumbai, 400012, India.
authors.forename: P
authors.initials: P
authors.lastname: Subramanian
authors.affiliation: Department of Medical Oncology, Tata Memorial Hospital, Mumbai, 400012, India.
authors.forename: Manju
authors.initials: M
authors.lastname: Sengar
authors.affiliation: Department of Medical Oncology, Tata Memorial Hospital, Mumbai, 400012, India.|Department of Clinical Hematology, Tata Medical Center, Kolkata, 700156, India.
authors.forename: Reena
authors.initials: R
authors.lastname: Nair
authors.affiliation: Department of Medical Oncology, Tata Memorial Hospital, Mumbai, 400012, India.
authors.forename: Hari
authors.initials: H
authors.lastname: Menon
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000493:pharmacokinetics; D059451:Biosimilar Pharmaceuticals / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000493:pharmacokinetics; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017711:Nonlinear Dynamics; D011241:Prednisone / Q000008:administration & dosage / Q000493:pharmacokinetics; D011446:Prospective Studies; D000069283:Rituximab / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015996:Survival Rate; D013997:Time Factors; D014750:Vincristine / Q000008:administration & dosage / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D059451:Biosimilar Pharmaceuticals; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
keywords: Biosimilar; DLBCL; MabThera; Population pharmacokinetics; Reditux; Rituximab