All of the following are true about rituximab except?: (A) Chimeric monoclonal antibody against CD-20 B cell antigen, (B) Most common side effect is infusion reaction, (C) First FDA drug approved for resistant lymphomas, (D) Dose independent pharmacokinetics
Answer is D. Ans. d. Dose independent pharmacokinetics (Ref: Harrison 19/e p2147,18/e p2749; Katzung 12/e p646; htt[://www.isdbweb. org/documents/file/1442_2pdf)Pharmacokinetics of rituximab (monoclonal antibodies) is dose dependent.'The rate of uptake and elimination of antibodies by target-mediated pathways is a function of dose and the expression level of the target, as well as a function of the kinetics of receptor internalization and intracellular catabolism http:// www.isdbweb.org/documents/file/1442_2.pdfRituximabRituximab is a murine-human monoclonal IgG1 (human Fc) that binds to the CD20 molecule on normal and malignant B lymphocytesQMechanism of Action:The mechanism of action includes complement-mediated lysis, antibody-dependent cellular cytotoxicity, and induction of apoptosis in the malignant lymphoma cellsQ.Indications:Approved for relapsed or refractory low-grade or follicular B cell non-Hodgkin's lymphomaQ.Approved for the treatment of refractory RA in combination with methotrexate and has been shown to be more effective for patients with seropositive than seronegative diseaseQ.Side-effects:Associated with mild-to- moderate infusion reactions as well as an increased risk of infectionQ.Notably, there have been isolated reports of a potentially lethal brain disorder, progressive multifocal leukoencephalopathy (PML), in association with rituximab therapy.It has been also shown to cause Tuberculosis.Pharmacokinetics:The rate of uptake and elimination of antibodies by target-mediated pathways is a function of dose and the expression level of the target, as well as a function of the kinetics of receptor internalization and intracellular catabolism.Monoclonal antibodies marketed for therapeutic useAntibodyIsotype/structurePrimary indicationAbciximabChimeric mouse/human FabPrevention of cardiac ischemic complicationsAdalimumabHuman lgG1Rheumatoid arthritisAlemtuzumabCDR-grafted rat/human IgG1B-cell chronic lymphocytic leukemiaBasiliximabChimeric mouse/human IgG1Prophylaxis of acute organ rejectionBevacizumabCDR-grafted mouse/human lgG1Colorectal, lung, and breast cancerCertolizumab pegotPEGylated FabCrohn's diseaseCetuximabChimeric mouse/human lgG1Head and neck cancer, colorectal cancerDaclizumabCDR-grafted mouse/human lgG1Prophylaxis of acute organ rejectionEculizumabCDR-grafted mouse/human lgG2/lgG4Paroxysmal nocturnal hemoglobinuriaEfalizumabCDR-grafted mouse/human lgG1PsoriasisGemtuzumab ozogamicinCDR-grafted mouse/human lgG4Acute myeloid leukemiaIbritumomab tiuxetanMurine lgG1Non-Hodgkin's lymphomaInfliximabChimeric mouse/human lgG1Rheumatoid arthritis, Crohn's diseaseMuromonab-CD3Murine lgG2aAcute organ rejectionNatalizumabCDR-grafted mouse/human lgG4Multiple sclerosisOmalizumabCDR-grafted mouse/human lgG1AsthmaPativizumabCDR-grafted mouse/human lgG1Prevention of respiratory tract diseasePanitumumabHuman lgG2Colorectal cancerRanibizumabCDR-grafted human IgG1 FabMacular degenerationRituximabChimeric mouse/human IgG1Non-Hodgkin's lymphoma, rheumatoid arthritisTositumomabMurine lgG2aNon-Hodgkin's lymphomaTrastuzumabCDR-grafted mouse/human lgG1Breast cancerCDR, complementarity determining region: IgG, immunoglobulin G.