Population Pharmacokinetics of Rituximab in Treatment-Naïve Chinese Patients With Diffuse Large B-cell Lymphoma During Induction Therapy: Clinical Implications.

This study aimed to establish and validate a population pharmacokinetic model for rituximab during induction therapy in treatment-naive patients with diffuse large B-cell lymphoma, identify covariates affecting key pharmacokinetic parameters, and predict exposure. This retrospective study included newly diagnosed patients receiving rituximab-containing induction regimens. Blood samples were collected before the next dose and after completion of the current dose across different chemotherapy cycles during the induction therapy; plasma concentrations were measured by chemiluminescent immunoassay. A nonlinear mixed-effects model was developed and externally validated. Individual parameters were obtained using empirical Bayesian methods, and first-cycle trough concentrations were predicted. For model building, 45 patients and 115 samples were included; external validation used 12 patients and 28 samples. Rituximab pharmacokinetics were described by a two-compartment model. Representative estimates were: clearance 0.0181 L/h, central volume 8.12 L, intercompartmental clearance 0.0213 L/h, peripheral volume 29.2 L. Albumin-globulin ratio was the final covariate and significantly affected clearance. Validation indicated good stability and predictive performance. Predicted first-cycle trough concentrations were below the reference efficacy threshold, and lower troughs were associated with smaller albumin-globulin ratios. This model quantified the effect of albumin-globulin ratio on clearance and suggests a risk of insufficient rituximab exposure during induction therapy, supporting future individualized dosing and therapeutic drug monitoring.