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.
Highlights
Primary nephrotic syndrome (NS) is the most common chronic glomerular disease in children (C (1978)
The following demographic and laboratory factors were collected for all patients at each visit: gender, proteinuria (PRO), body weight (BW), height (HT), body surface area (BSA), age, age at onset, NS duration, serum albumin (ALB), serum total cholesterol (TCH), serum creatinine (Scr), creatinine clearance rate (CLCR, where k 0.413 for children 1–13 years old and 0.70 for males between the ages of 13 and 20) (Schwartz et al, 2009), blood urea nitrogen (BUN), cystatin C (CysC), and proteinuria-to-creatinine ratio (PRO/CR)
The study population consisted of 14 pediatric patients with frequent-relapsing nephrotic syndrome (FRNS)/steroid-dependent nephrotic syndrome (SDNS)
Summary
Primary nephrotic syndrome (NS) is the most common chronic glomerular disease in children (C (1978). Despite the fact that approximately 80% of these children are recognized as steroid-sensitive nephrotic syndrome (SSNS) (C (1981). The primary, 1981), up to 50% of these SSNS patients will develop to frequent-relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS) (Schulman et al, 1988). These children often experience steroid toxicities and complications of immunosuppression (Park and Shin, 2011), suggesting that there is an urgent need to develop new treatments for children with FRNS/SDNS.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
