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Antibody pharmacokinetics

Therapeutic monoclonal antibodies are widely recognized to be a most promising means to treat an increasing number of human diseases, including cancers and autoimmunity. To a large extent, the efficacy of monoclonal antibody treatment is because IgG antibodies have greatly extended persistence in vivo. However, conventional rodent models do not mirror human antibody pharmacokinetics. The key molecule responsible for the extended persistence antibodies is the major histocompatibility complex class I family Fc receptor, FcRn. We describe human FcRn transgenic mouse models and how they can be exploited productively for the preclinical pharmacokinetic evaluation of therapeutic antibodies. [Pg.93]

Wang W, Wang EQ, Balthasar JP. Monoclonal antibody pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther. 2008 84(5) 548-558. [Pg.342]

The particular complexities of antibody pharmacokinetics and their relationship to pharmacodynamics have been thoroughly reviewed by Lobo and coworkers [16]. Many of the characteristics discussed above for macromolecules in general also apply in the case of antibodies. Thus, absorption following subcutaneous or intramuscular administration may be slow, with involvement of lymphatic transport, and attainment of peak blood concentrations may take days. Although absorption of antibodies from the gastrointestinal tract following oral administration to adult humans is very limited, absorption of IgG from the gastrointestinal tract of neonates of several species has been demonstrated [34]. This absorption occurs via interaction with the neonatal receptor for... [Pg.20]

Lobo E etal. (2004). Antibody pharmacokinetics and pharmacodynamics. /Pliorm Sci 93 2645-2668. [Pg.390]

Lobo ED, Hansen RJ, Balthasar JP. Antibody pharmacokinetics and pharmacodynamics. J Pharm Sci 2004 93(11) 2645—2668. [Pg.642]

Colburn, W.A. Specific antibodies and Fab fragments to alter the pharmacokinetics and reverse the pharmacological/toxicological effects of drugs. Drug Metab Rev 11(2) 223-262, 1980. [Pg.137]

Ochs, H.R., and Smith, T.W. Reversal of advanced digitoxin toxicity and modification of pharmacokinetics by specific antibodies and Fab fragments. J. Clin Tnvest 60 1303-1313, 1977. [Pg.138]

Alemtuzumab is the antibody to the CD52 receptor present on B and T lymphocytes. The pharmacokinetics of alemtuzumab demonstrate a terminal half-life of 7 days. Alemtuzumab has shown clinical activity in the treatment of chronic lymphocytic leukemia. Severe and prolonged (6 months) immunosuppression may result, which necessitates prophylaxis with cotrimox-azole and antivirals to prevent opportunistic infections. [Pg.1294]

Cetuximab is a human/mouse antibody that binds to the epidermal growth factor receptor to block its stimulation. The pharmacokinetics of cetuximab demonstrate a volume of distribution that approximates the vascular space and a terminal half-life of 70 to 100 hours. Cetuximab has shown clinical activity in the treatment of colorectal cancer. An acnelike rash may appear on the face and upper torso 1 to 3 weeks after the start of therapy. Other side effects include hypersensitivity reactions, interstitial lung disease, fever, malaise, diarrhea, abdominal pain, and nausea and vomiting. [Pg.1294]

Rituximab is a monoclonal antibody to the CD20 receptor expressed on the surface of B lymphocytes the presence of the antibody is determined during flow cytometry of the tumor cells. Cell death results from antibody-dependent cellular cytotoxicity. The pharmacokinetics of rituximab are best described by a two-compartment model, with a terminal half-life of 76 hours after the first infusion and a terminal half-life of 205 hours after the fourth dose.36 Rituximab has shown clinical activity in the treatment of B-cell lymphomas that are CD20+. Side effects include hypersensitivity reactions, hypotension, fevers, chills, rash, headache, and mild nausea and vomiting. [Pg.1294]

Pharmacokinetic studies indicate the product displays two-compartment behaviour, with a distribution phase (half-life 2-5 min) and a terminal phase (half-life 70-80 min). Development of antibodies to the product significantly impacts upon clearance rates. [Pg.251]

Joshi, A., Bauer, R., Kuebler, P, White, M., Leddy, C., Compton, P., Garovoy, M., Kwon, P., Walicke, P., and Dedrick, R. 2006. An overview of the pharmacokinetics and pharmacodynamics of efalizumab a monoclonal antibody approved for use in psoriasis. Journal of Clinical Pharmacology 46(1), 10-20. [Pg.417]


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Pharmacokinetics of Monoclonal Antibodies

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