Rituximab Exhibits Altered Pharmacokinetics in Patients With Membranous Nephropathy

Uma Fogueri, Wisit Cheungapasitporn, David Bourne, Fernando Custodio Fervenza, Melanie S. Joy

Research output: Contribution to journalArticle

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Abstract

Background: Rituximab (RTX) is a chimeric monoclonal anti-CD20 antibody used off-label in the treatment of membranous nephropathy (MN). Unfortunately, limited information is available on the pharmacokinetics of therapeutic proteins such as RTX in patients with glomerular kidney diseases. Objective: The current study evaluated RTX pharmacokinetics in patients with MN (n = 20) who received 4 RTX weekly intravenous infusions (375 mg/m2) over a month, with a repeat of the identical treatment at 6 months. Baseline patient characteristics were gender (17 male/3 female), age (49 ± 13 years), and body surface area (2.2 ± 0.24 m2). Methods: Compartmental pharmacokinetic analyses were conducted using Phoenix, and comparisons of these parameters were made between the MN patients and published data from 2 reference populations without kidney diseases (follicular lymphoma and autoimmune disorders). Results: Patients with MN exhibited a shorter half-life, reduced volume of central compartment, decreased area under the serum concentration-time curve (exposure), and increased RTX clearance from the central compartment versus previous reports in the reference patient populations. Conclusions and Relevance: These results suggest that shorter half-life and lower exposures to RTX in patients with MN may necessitate higher doses and/or changes to dosing frequency to optimize the relationships between serum concentrations and therapeutic effects.

Original languageEnglish (US)
JournalAnnals of Pharmacotherapy
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Membranous Glomerulonephritis
Pharmacokinetics
Kidney Diseases
Half-Life
Follicular Lymphoma
Body Surface Area
Therapeutic Uses
Rituximab
Serum
Intravenous Infusions
Population
Anti-Idiotypic Antibodies
Therapeutics
Monoclonal Antibodies

Keywords

  • clearance
  • membranous nephropathy
  • monoclonal antibody
  • pharmacokinetics
  • rituximab

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Rituximab Exhibits Altered Pharmacokinetics in Patients With Membranous Nephropathy. / Fogueri, Uma; Cheungapasitporn, Wisit; Bourne, David; Fervenza, Fernando Custodio; Joy, Melanie S.

In: Annals of Pharmacotherapy, 01.01.2018.

Research output: Contribution to journalArticle

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