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Pharmacokinetics/dynamics of 5c8, a monoclonal antibody to CD154 (CD40 ligand) suppression of an immune response in monkeys

Gobburu, J V ; Tenhoor, C ; Rogge, M C ; Frazier, D E ; Thomas, D ; Benjamin, C ; Hess, D M ; Jusko, W J

The Journal of pharmacology and experimental therapeutics, August 1998, Vol.286(2), pp.925-30 [Rivista Peer Reviewed]

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  • Titolo:
    Pharmacokinetics/dynamics of 5c8, a monoclonal antibody to CD154 (CD40 ligand) suppression of an immune response in monkeys
  • Autore: Gobburu, J V ; Tenhoor, C ; Rogge, M C ; Frazier, D E ; Thomas, D ; Benjamin, C ; Hess, D M ; Jusko, W J
  • Note di contenuto: The pharmacokinetics and pharmacodynamics (PK/PD) of chimeric (Ch5c8) and humanized (Hu5c8) 5c8, a monoclonal antibody that binds CD154 (CD40 ligand), thus blocking the interaction between CD40 and CD154, were investigated in cynomolgus monkeys. Single-dose groups (n = 3 animals per dose) received saline, 0.2, 1, 5 or 20 mg/kg i.v. doses of Hu5c8. The repeat-dose groups (n = 4 animals) received 0 or 5 mg/kg i.v. doses of Ch5c8 or Hu5c8 on days 1, 2, 3, 5, 7 and 9. The single-dose PK parameters showed dose proportionality, with a terminal half-life of 300 h, a volume of distribution at steady state of 73 ml/kg and clearance of 0.2 ml.h-1.kg-1. The repeat-dose regimen produced a longer terminal half-life (500 h) and lower clearance (0.13 ml.h-1.kg-1) than in the single-dose groups. The antibody titer to tetanus toxoid (ATT) challenge served as the immunodynamic marker. The primary ATT response consisted of a latent phase of approximately 10 days, during which the immune system was processing...
  • Fa parte di: The Journal of pharmacology and experimental therapeutics, August 1998, Vol.286(2), pp.925-30
  • Soggetti: Antibodies, Monoclonal -- Pharmacokinetics ; Cd40 Antigens -- Immunology ; Immunosuppressive Agents -- Pharmacokinetics
  • Lingua: Inglese
  • Tipo: Articolo
  • Identificativo: ISSN: 0022-3565 ; PMID: 9694951 Version:1
  • Fonte: MEDLINE/PubMed (U.S. National Library of Medicine)

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