Rituximab

pharmacological · immune-hematologic · IV · Subcutaneous

Rituximab. Chimeric mouse/human anti-CD20 IgG1 monoclonal antibody — depletes CD20+ B cells via ADCC + CDC + apoptosis. First approved oncology mAb… IV half-life 19 d.

Chimeric mouse/human anti-CD20 IgG1 monoclonal antibody — depletes CD20+ B cells via ADCC + CDC + apoptosis. First approved oncology mAb (1997). Indications: non-Hodgkin lymphoma, CLL, rheumatoid arthritis, granulomatosis with polyangiitis / microscopic polyangiitis, pemphigus vulgaris, MS (off-label), various autoimmune diseases. Biologic PK — long IgG-class t½ ~22 days, IgG salvage / FcRn-mediated clearance, not metabolized by CYPs. PK (Rozman 2017 popPK PMID:28339136 + Rituxan label): IV-only mAb. Two-compartment model with time-varying clearance. V1 (central) 2.7-3.1 L, V/F apparent ~5 L. Two clearance routes: nonspecific CL1 0.14 L/day (Fc-receptor-mediated reticuloendothelial uptake — slow + constant) + specific CL2 0.59 L/day (B-cell/tumor-burden mediated — declines as B cells are depleted). Median terminal t½ 22 days (range 6-52). Steady state by ~16-24 weeks of weekly dosing in NHL protocol.

PK: A RANGE INTERIOR REPLACED BY A STATED MEAN THAT WAS ALREADY IN THIS RECORD REFERENCES. The stored half-life appears in its citation only as the inside of a spread — "a long elimination half-life of approximately 3 weeks (range, 248-859 hours)" — while the second reference this record already carries states a point value outright: "The elimination half-life at steady state of rituximab in all patients was estimated to be 19.2 (+/- 15.2%) days". THE VOLUME IS UNSOURCED AND IS DELIBERATELY NOT REPLACED: the only clearance either paper offers is itself a RANGE, "The total systemic clearance ranged between 3.1 and 11.9 mL/hr/m", and storing a volume derived from its midpoint would commit precisely the defect this audit keeps finding. At the corrected half-life the clearance the record implies sits just below the low end of that verbatim range, which is a near-miss rather than a defect and is recorded as one. Its citation also states plainly that "Rituximab disposition was characterized by a 2-exponential decay", so the usual one-compartment caveat applies: exposure is carried and the early distribution phase is not.

Pharmacokinetics

Sources: PMID:20555126