Pharmacokinetics of rituximab in a pediatric patient with therapy-resistant nephrotic syndrome

Abstract

BackgroundRituximab (RTX) has recently been introduced as a second-line therapy for nephrotic syndrome in children. Studies show that RTX given during the nephrotic state may be less effective than treatment during a non-nephrotic state, possibly due to loss of RTX in the urine.Case-Diagnosis/TreatmentWe describe a 10-year-old boy with steroid-resistant nephrotic syndrome (SRNS) treated with RTX during a phase of active non-selective proteinuria. The serum half-life of RTX in this patient was less than 1 day compared to 20 days in patients without protein losses. Urinary clearance was at least 25 %, compared to approximately 0 % in control patients. However, RTX loss in the urine, as well as in pleural effusion and ascites, only partly explains the rapid drop in the serum RTX concentration of this patient.ConclusionsSerum half-life of RTX can be extremely short, partly due to excessive urinary losses in therapy-resistant nephrotic syndrome with non-selective proteinuria, as seen in our patient. These findings may help to explain the poor results of RTX treatment in patients with active proteinuria.Electronic supplementary materialThe online version of this article (doi:10.1007/s00467-015-3120-8) contains supplementary material, which is available to authorized users.

A Brief Overview Of Childhood Nephrotic Syndrome: Review

“…Bundan başka, yeni yapılan bir çalışmada SDiNS'li ço-cuklarda rituksumabın idrarla kaybı ve üçüncü boşluklara (asit, plevral efüzyon) dağılımı nedeni ile yarı ömrü çok kısa bulunmuş (normalde 20 gün, SDiNS'de <1 gün) ve bu ajanın SDiNS'de başarısız-lığında bu durum bir etken olarak ileri sürülmüş-tür. 79 …”

Commonality of rituximab pharmacokinetic disposition in nephrotic syndrome and autoimmune cytopenias in chronic lymphocytic leukemia patients

“…In this patient, the half-life of rituximab was reported to be less than a day [1]. The use of population pharmacokinetic modeling that factored in elimination and distributive sites enabled delineation of the pharmacokinetic profile of rituximab in the patient with nephrotic syndrome [1]. Interestingly, Mo et al reported the pharmacokinetics of rituximab in autoimmune cytopenias exhibited by chronic lymphocytic leukemia (CLL) patients; where a rapid clearance of rituximab was observed in all the patients during the first cycle of treatment rendering undetectable trough concentrations of rituximab [2].…”

“…The authors postulated the existence of other possible mechanisms that may possibly explain the rapid clearance of rituximab. In this patient, the half-life of rituximab was reported to be less than a day [1]. The use of population pharmacokinetic modeling that factored in elimination and distributive sites enabled delineation of the pharmacokinetic profile of rituximab in the patient with nephrotic syndrome [1].…”

“…Recently, Counsilman et al [1] reported for the first time the pharmacokinetic disposition of rituximab in a patient with nephrotic syndrome accompanied by non-selective proteinuria [1]. The pharmacokinetics of rituximab were characterized by a rapid clearance and low serum levels due to urinary loss and excessive distribution of rituximab into pleural effusion and ascites [1].…”

“…The pharmacokinetics of rituximab were characterized by a rapid clearance and low serum levels due to urinary loss and excessive distribution of rituximab into pleural effusion and ascites [1]. The authors postulated the existence of other possible mechanisms that may possibly explain the rapid clearance of rituximab.…”