Rituximab Exhibits Altered Pharmacokinetics in Patients With Membranous Nephropathy.

Abstract

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. 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). 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). 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. 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.