Background and importance Rituximab (RTX) is a monoclonal antibody used to treat various conditions including glomerular diseases (GD) as an off-label indication. There is high variability in RTX pharmacokinetics (PK) and it has scarcely being studied in cases of nephrotic syndrome (NS) (Fogueri et al, 2019). We report the PK analysis of RTX in a case of GD and measure RTX excretion in urine.
Aim and objectives We present a 72-year-old male with hypertension, dislipemia and obesity (81 kg) diagnosed with membranous nephropathy in September2020. Usual medication included magnesium, amlodipine and ezetimibe.
Material and methods In October 2020 the patient suffered severe NS (proteinuria:16 g/24 hours, hypoalbuminaemia: 2.1g/mL, hypercholesterolaemia: 406 mg/dL) and RTX was prescribed, according to available knowledge at the time: 1 g days 1 and 15.
Routine blood and 24-hour urine samples were collected. RTX was measured in serum with an ELISA kit: Lisa-Tracker-Rituximab (Theradiag).The quantitative determination of RTX in urine was performed using in-house standards and urine samples diluted to 1/100 in Phosphate-Tween Buffer.
RTX’s PK analysis was done using a monocompartimental model and nonlinear regression (Winnolin). RTX maximum concentration (Cmax), distribution volume (Vd), clearance (Cl) and half-life (t1/2) were determined.
Results RTX plasma concentration: 0 µg/mL at day 1 (d1) (pre-dose), 26.38 µg/mL at d 7. 7.93µg/ml at d15 (pre-dose), 64.99 µg/mL at d15 (post-dose) and 3.72 µg/dL at d28.
RTX urine concentration: 0.18 µg/mL at d1 (pre-dose), 2.12 µg/mL at d7 and 0.18 µg/mL at d15.
PK analysis: Cmax=92.0 µg/mL, Vd=135.1 mL/kg, Cl=1.075 mL/kg/hour, t1/2= 88.91 hours=3.7 day.
By d7 there were 93.2 mg of RTX in the body and 17.8 mg were eliminated that day. Considering a 1500 ml/24 hour urine production, 3.18 mg of RTX were excreted at d7, 3.4% of RTX in plasma was excreted by urine every 24 hours and urine excretion justified 17.9% of RTX elimination.
Tacrolimus was initiated in December 2020 due to persistent NS.
Ten months after RTX administration the patient remains in complete remission (proteinuria: 0.5 g/24 hours, serum albumin: 3.8 g/ml, serum cholesterol: 237 mg/dL).
Conclusion and relevance The patient’s RTX Vd was increased which may be due to NS-related oedema; Cmax was lower, Cl was increased and t1/2 was notably shorter than reported values, which can be justified by RTX elimination in urine. RTX PKs are altered in cases of NS, leading to a reduced exposure. RTX may be aberrantly eliminated in urine in cases of NS and its concentration can be measured with ELISA.
Conflict of interest No conflict of interest
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.