Speaker
Description
Background: Rituximab (RTX) is widely used off-label for pediatric patients with frequently relapsing or steroid-dependent nephrotic syndrome (FRNS/SDNS), yet dosing remains extrapolated from B-cell lymphoma regimens. This study characterizes population pharmacokinetics and exposure-response to inform optimal pediatric dosing.
Methods: Thirty-one pediatric patients with FRNS/SDNS were enrolled from Nanfang Hospital and administered RTX at 375 mg/m². Blood samples were collected at 6 time points, and the concentration of RTX was determined by ELISA. The population pharmacokinetic model was developed using Phoenix NLME (V.7.0; Certara), employing the first-order conditional estimation with the extended least squares method throughout the process. Meanwhile, the correlation between rituximab exposure and CD20+ lymphocyte counts was analyzed using Spearman’s correlation coefficient.
Results: A total of 197 plasma samples were collected to establish the population pharmacokinetic model. The one-compartment model was selected as the structural model based on lower OFV, AIC, and BIC values compared with the two-compartment model. The multiplicative error model better described residual variability. Age and body weight were identified as significant covariates, decreasing OFV from 1265.19 to 1244.02. The final model demonstrated excellent predictive performance. Notably, AUClast of RTX was significantly lower in relapsed patients, with a moderate positive correlation observed between CD20⁺ lymphocyte reconstitution time and AUClast (r = 0.5082).
Conclusion: This study provides a population PK model of rituximab in Chinese pediatric FRNS/SDNS patients, serving as a reference for future individualized dosing strategies based on age and weight.
