title: Population pharmacokinetics of rituximab with or without plasmapheresis in kidney patients with antibody-mediated disease.
abstract: OBJECTIVE
  Both rituximab and plasmapheresis can be associated in the treatment of immune-mediated kidney diseases. The real impact of plasmapheresis on rituximab pharmacokinetics is unknown. The aim of this study was to compare rituximab pharmacokinetics between patients requiring plasmapheresis and others without plasmapheresis.
  
  
  METHODS
  The study included 20 patients receiving one or several infusions of rituximab. In 10 patients, plasmapheresis sessions were also performed (between two and six sessions per patient). Rituximab concentrations were measured in blood samples in all patients and in discarded plasma obtained by plasmapheresis using an enzyme-linked immunosorbent assay method. Data were analysed according to a population pharmacokinetic approach.
  
  
  RESULTS
  The mean percentage of rituximab removed during the first plasmapheresis session ranged between 47 and 54% when plasmapheresis was performed between 24 and 72 h after rituximab infusion. Rituximab pharmacokinetics was adequately described by a two-compartment model with first-order elimination. Plasmapheresis had a significant impact on rituximab pharmacokinetics, with an increase of rituximab clearance by a factor of 261 (95% confidence interval 146-376), i.e. from 6.64 to 1733 ml h(-1) . Plasmapheresis performed 24 h after rituximab infusion decreased the rituximab area under the curve by 26%.
  
  
  CONCLUSIONS
  Plasmapheresis removed an important amount of rituximab when performed less than 3 days after infusion. The removal of rituximab led to a significant decrease of the area under the curve. This pharmacokinetic observation should be taken into account for rituximab dosing, e.g. an additional third rituximab infusion may be recommended when three plasmapheresis sessions are performed after the first rituximab infusion.
authors: Pharmacie, Centre Hospitalier Universitaire, Toulouse, France; EA4553, Université Paul Sabatier and Institut Claudius-Regaud, Toulouse, France.
authors: Florent
authors: F
authors: Puisset
authors: Mélanie
authors: M
authors: White-Koning
authors: Nassim
authors: N
authors: Kamar
authors: Antoine
authors: A
authors: Huart
authors: Frédérique
authors: F
authors: Haberer
authors: Hélène
authors: H
authors: Blasco
authors: Chantal
authors: C
authors: Le Guellec
authors: Thierry
authors: T
authors: Lafont
authors: Anaïs
authors: A
authors: Grand
authors: Lionel
authors: L
authors: Rostaing
authors: Etienne
authors: E
authors: Chatelut
authors: Jacques
authors: J
authors: Pourrat
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000493:pharmacokinetics*; D007674:Kidney Diseases / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010956:Plasmapheresis; D000069283:Rituximab; D013997:Time Factors
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D000069283:Rituximab
keywords: pharmacokinetics; plasmapheresis; rituximab