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Population Pharmacokinetics of Rituximab in Patients With Chronic Lymphocytic Leukemia
Author(s) -
Li Jing,
Zhi Jianguo,
Wenger Michael,
Valente Nancy,
Dmoszynska Anna,
Robak Tadeusz,
Mangat Ranvir,
Joshi Amita,
Visich Jennifer
Publication year - 2012
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270011430506
Subject(s) - fludarabine , rituximab , cyclophosphamide , chronic lymphocytic leukemia , pharmacokinetics , medicine , population , volume of distribution , pharmacology , oncology , immunology , lymphoma , leukemia , chemotherapy , environmental health
This retrospective analysis characterizes rituximab population pharmacokinetics in combination with fludarabine and cyclophosphamide and its effect on fludarabine and cyclophosphamide disposition in chronic lymphocytic leukemia (CLL) patients. Rituximab concentration data were well described by a 2‐compartment model comprising a time‐varying clearance component related to the target‐mediated clearance pathway and a constant clearance component reflecting catabolic elimination pathway. Marked differences were observed compared to pharmacokinetic parameters for non‐Hodgkin lymphoma (NHL) obtained previously: in CLL, time‐varying clearance at time zero (CL 2 ) was faster, volumes of distribution (V 1 and V 2 ) were larger, and rate of change (K des ) from the target‐mediated clearance pathway to catabolic elimination was lower than NHL. Fludarabine and cyclophosphamide disposition showed no apparent change when co‐administered with rituximab. A positive correlation between pharmacokinetic parameters and clinical response was observed, supporting the use of the higher rituximab dose of 500 mg/m 2 in CLL patients (vs 375 mg/m 2 in NHL) to achieve an effective clinical response.