Population pharmacokinetics of rituximab in patients with chronic lymphocytic leukemia.
J Clin Pharmacol
; 52(12): 1918-26, 2012 Dec.
Article
en En
| MEDLINE
| ID: mdl-22235140
ABSTRACT
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 targetmediated 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Leucemia Linfocítica Crónica de Células B
/
Protocolos de Quimioterapia Combinada Antineoplásica
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Clin Pharmacol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos