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Nonlinear pharmacokinetics of rituximab in non-Hodgkin lymphomas: A pilot study.

Ternant, David; Monjanel, Hélène; Venel, Yann; Prunier-Aesch, Caroline; Arbion, Flavie; Colombat, Philippe; Paintaud, Gilles; Gyan, Emmanuel.
Br J Clin Pharmacol; 85(9): 2002-2010, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31112622


Rituximab is an anti-CD20 monoclonal antibody approved in non-Hodgkin lymphoma (NHL). This study aimed to assess the relationship between antigen mass and nonlinear pharmacokinetics of rituximab in NHL patients.


In a retrospective cohort of 25 NHL patients treated with rituximab, antigen mass was assessed at baseline by measuring metabolic tumour volume (MTV) by positron emission tomography. Rituximab pharmacokinetics was described using a semimechanistic 2-compartment model including a latent target antigen. Rituximab target-mediated elimination was described as irreversible binding between rituximab and it target. Histology (follicular or diffuse large B-cell lymphomas), initial MTV and body weight were tested as covariates on pharmacokinetic parameters.


The model allowed a satisfactory description of rituximab serum concentrations. Target-mediated elimination was maximum at the beginning of treatment and became negligible towards the end of follow-up. The second-order elimination of rituximab due to target binding and complex elimination increased with baseline MTV. Central volume of distribution increased with body weight (P = .022) and baseline MTV (P = .005).


This study quantified for the first time the target-mediated elimination of rituximab in NHL patients and confirmed rituximab retention by antigen mass.
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