Population Pharmacokinetics of Rituximab in Pediatric Patients With Frequent-Relapsing or Steroid-Dependent Nephrotic Syndrome

Yewei Chen; Qian Shen; Min Dong; Ye Xiong; Hong Xu; Zhiping Li

doi:10.3389/fphar.2021.725665

Population Pharmacokinetics of Rituximab in Pediatric Patients With Frequent-Relapsing or Steroid-Dependent Nephrotic Syndrome

Front Pharmacol. 2021 Sep 2:12:725665. doi: 10.3389/fphar.2021.725665. eCollection 2021.

Authors

Yewei Chen¹, Qian Shen², Min Dong^{3

4}, Ye Xiong³, Hong Xu², Zhiping Li¹

Affiliations

¹ Department of Pharmacy, Children's Hospital of Fudan University, Shanghai, China.
² Department of Nephrology, Children's Hospital of Fudan University, Shanghai, China.
³ Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
⁴ Department of Pediatrics, University of Cincinnati, Cincinnati, OH, United States.

Abstract

Objectives: Rituximab is frequently used off-label for the treatment of frequent-relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS), but the relapse rate remained high and the dosing regimen varied widely. The objective of this study was to characterize rituximab pharmacokinetics (PK) in pediatric patients with FRNS/SDNS, and to investigate the differences in rituximab PK between patients with FRNS/SDNS and other disease populations. Methods: Fourteen pediatric patients received rituximab for FRNS/SDNS treatment were enrolled in a prospective, open-label, single-center PK study. A population PK model of rituximab was developed and validated, and PK parameters were derived for quantitative evaluation. Results: A two-compartment PK model best described the data. Body surface area was the most significant covariate for both central clearance (CL) and apparent central volume of distribution (V₁). Patients with FRNS/SDNS exhibited a clinically relevant increase in rituximab CL compared to patient population with non-Hodgkin's lymphoma (NHL). Conclusion: This pilot study indicated that higher doses or more frequent regimens of rituximab may be required for optimal therapeutic effects in patients with FRNS/SDNS. Further clinical studies with more patients are warranted to confirm this result.

Keywords: children; dosing; nephrotic syndrome; pharmacokinetics; rituximab.