David Ternant1,2, Hélène Monjanel3, Yann Venel4, Caroline Prunier-Aesch5, Flavie Arbion6, Philippe Colombat3,7, Gilles Paintaud1,2, Emmanuel Gyan3,7. 1. EA 7501 GICC, Université de Tours, Tours, France. 2. Service de Pharmacologie Médicale, CHRU de Tours, Tours, France. 3. Hématologie et Thérapie Cellulaire, CHRU de Tours, Tours, France. 4. Médecine Nucléaire, CHRU de Tours, France. 5. Chambray Les Tours, Médecine Nucléaire Tourangelle, France. 6. Service d'Anatomie et Cytologie Pathologiques, CHRU de Tours, Tours, France. 7. ERL CNRS 7001 LNOx, Université de Tours, Tours, France.
Abstract
AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: This study quantified for the first time the target-mediated elimination of rituximab in NHL patients and confirmed rituximab retention by antigen mass.
AIMS: 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 NHLpatients. METHODS: In a retrospective cohort of 25 NHLpatients 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. RESULTS: 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). CONCLUSIONS: This study quantified for the first time the target-mediated elimination of rituximab in NHLpatients and confirmed rituximab retention by antigen mass.
Authors: Stephen Ph Alexander; Eamonn Kelly; Neil V Marrion; John A Peters; Elena Faccenda; Simon D Harding; Adam J Pawson; Joanna L Sharman; Christopher Southan; O Peter Buneman; John A Cidlowski; Arthur Christopoulos; Anthony P Davenport; Doriano Fabbro; Michael Spedding; Jörg Striessnig; Jamie A Davies Journal: Br J Pharmacol Date: 2017-12 Impact factor: 8.739
Authors: Jan Koedam; Martin Wermke; Armin Ehninger; Marc Cartellieri; Gerhard Ehninger Journal: Curr Opin Hematol Date: 2022-03-01 Impact factor: 3.284