Clinical Pharmacokinetics of Therapeutic Monoclonal Antibodies View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2010-08

AUTHORS

Ron J. Keizer, Alwin D. R. Huitema, Jan H. M. Schellens, Jos H. Beijnen

ABSTRACT

Monoclonal antibodies (mAbs) have been used in the treatment of various diseases for over 20 years and combine high specificity with generally low toxicity. Their pharmacokinetic properties differ markedly from those of non-antibody-type drugs, and these properties can have important clinical implications. mAbs are administered intravenously, intramuscularly or subcutaneously. Oral administration is precluded by the molecular size, hydrophilicity and gastric degradation of mAbs. Distribution into tissue is slow because of the molecular size of mAbs, and volumes of distribution are generally low. mAbs are metabolized to peptides and amino acids in several tissues, by circulating phagocytic cells or by their target antigen-containing cells. Antibodies and endogenous immunoglobulins are protected from degradation by binding to protective receptors (the neonatal Fc-receptor [FcRn]), which explains their long elimination half-lives (up to 4 weeks). Population pharmacokinetic analyses have been applied in assessing covariates in the disposition of mAbs. Both linear and nonlinear elimination have been reported for mAbs, which is probably caused by target-mediated disposition. Possible factors influencing elimination of mAbs include the amount of the target antigen, immune reactions to the antibody and patient demographics. Bodyweight and/or body surface area are generally related to clearance of mAbs, but clinical relevance is often low. Metabolic drug-drug interactions are rare for mAbs. Exposure-response relationships have been described for some mAbs. In conclusion, the parenteral administration, slow tissue distribution and long elimination half-life are the most pronounced clinical pharmacokinetic characteristics of mAbs. More... »

PAGES

493-507

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.2165/11531280-000000000-00000

    DOI

    http://dx.doi.org/10.2165/11531280-000000000-00000

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1033453107

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/20608753


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