Pharmacokinetic profiling of rituximab in glomerular diseases: key determinants and implications for personalized therapy

利妥昔单抗在肾小球疾病中的药代动力学特征分析:关键决定因素及其对个体化治疗的意义

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Abstract

Rituximab demonstrates significant efficacy in the treatment of glomerular diseases; however, considerable heterogeneity in clinical responses is observed. This variability is largely attributable to the complex pharmacokinetic profile of rituximab, which is a key determinant of interindividual differences in treatment outcomes. To systematically elucidate the pharmacokinetic characteristics of rituximab across different glomerulopathies and their association with clinical efficacy, this review synthesizes current literature, with a focus on analyzing the impact of key variables, including proteinuria, anti-drug antibodies, and competition for the neonatal Fc receptor, on drug clearance. Furthermore, we compare the dynamic serum concentration profiles and therapeutic outcomes of rituximab in membranous nephropathy, minimal change disease, and lupus nephritis. The findings reveal that the pharmacokinetics of rituximab in patients with glomerular diseases are highly heterogeneous, modulated by both disease-specific factors (for example, damage to the glomerular filtration barrier leads to the urinary loss of proteins) and patient-intrinsic factors (such as polymorphisms in the Neonatal Fc Receptor gene). Available evidence indicates that subtherapeutic drug exposure is closely associated with incomplete B-cell depletion and suboptimal clinical remission. Based on these insights, we identify critical monitoring timepoints for early detection of insufficient exposure (for instance, months 2-3 in membranous nephropathy and month 2 in lupus nephritis). Nevertheless, current data are predominantly derived from retrospective and small-sample studies, and evidence-based target concentration ranges specific to glomerular diseases remain undefined. This review aims to provide an evidence-based rationale and practical recommendations for personalized dosing strategies guided by therapeutic drug monitoring.

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