Antigenic burden and serum IgG concentrations influence rituximab pharmacokinetics in rheumatoid arthritis patients.

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  • Additional Information
    • Source:
      Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 7503323 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2125 (Electronic) Linking ISSN: 03065251 NLM ISO Abbreviation: Br J Clin Pharmacol Subsets: MEDLINE
    • Publication Information:
      Publication: Oxford : Wiley-Blackwell
      Original Publication: London, Macmillan Journals Ltd.
    • Subject Terms:
      Antigens, CD20/*blood ; Antirheumatic Agents/*pharmacokinetics ; Arthritis, Rheumatoid/*drug therapy ; B-Lymphocytes/*metabolism ; Immunoglobulin G/*blood ; Rituximab/*pharmacokinetics; Adult ; Aged ; Aged, 80 and over ; Antigens, CD19/metabolism ; Antigens, CD20/metabolism ; Antirheumatic Agents/therapeutic use ; Arthritis, Rheumatoid/blood ; Body Surface Area ; Female ; Humans ; Lymphocyte Count ; Male ; Middle Aged ; Retrospective Studies ; Rituximab/therapeutic use ; Sex Factors
    • Abstract:
      Aims: Rituximab is a monoclonal antibody directed against CD20, which is approved in rheumatoid arthritis (RA). This study aimed at assessing the influence of CD19+ cell counts as target-antigen amount, and of immunoglobulin G (IgG) serum concentrations on rituximab pharmacokinetics in RA patients.
      Methods: In a cohort of 64 RA patients who had received repetitive courses of rituximab, the influence of CD19+ cell count, IgG serum concentration, body surface area, sex and disease activity score in 28 joints on rituximab pharmacokinetic parameters was assessed using a population pharmacokinetic analysis.
      Results: A two-compartment model, with first-order distribution and elimination best described the data. The volume of distribution of central compartment and clearance of rituximab were estimated at 4.7 l and 0.56 l day -1 , respectively. Distribution and elimination half-lives were 0.9 days and 17.3 days, respectively. As expected, the central volume of distribution increased with body surface area (P = 0.012) and was higher in male than in female (P = 0.004). We found that the elimination rate constant (k 10 ) increased with CD19+ count (P = 0.00022) and IgG concentration (P = 7.4 × 10 -8 ), and that k 10 decreased with time (P = 0.00015), partly explained by a change in target-antigen amount.
      Conclusions: The association between CD19+ count and k 10 may be explained by target-mediated drug disposition, while the association between IgG serum concentration and k 10 may be explained by a saturation of the neonatal Fc receptor at high IgG concentrations, resulting in decreased recycling of rituximab.
      (© 2017 The British Pharmacological Society.)
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    • Contributed Indexing:
      Keywords: elimination rate constant; immunoglobulin; pharmacokinetics; rheumatoid arthritis; rituximab
    • Accession Number:
      0 (Antigens, CD19)
      0 (Antigens, CD20)
      0 (Antirheumatic Agents)
      0 (CD19 molecule, human)
      0 (Immunoglobulin G)
      4F4X42SYQ6 (Rituximab)
    • Publication Date:
      Date Created: 20170224 Date Completed: 20180412 Latest Revision: 20220316
    • Publication Date:
      20221213
    • Accession Number:
      PMC5510084
    • Accession Number:
      10.1111/bcp.13270
    • Accession Number:
      28230269