Rituximab Exhibits Altered Pharmacokinetics in Patients With Membranous Nephropathy

Ann Pharmacother. 2019 Apr;53(4):357-363. doi: 10.1177/1060028018803587. Epub 2018 Oct 8.


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.

Keywords: clearance; membranous nephropathy; monoclonal antibody; pharmacokinetics; rituximab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoimmune Diseases / drug therapy
  • Female
  • Glomerulonephritis, Membranous / blood*
  • Glomerulonephritis, Membranous / immunology
  • Half-Life
  • Humans
  • Infusions, Intravenous
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Off-Label Use
  • Rituximab / administration & dosage
  • Rituximab / blood*


  • Rituximab