Clinical Pharmacokinetics of Therapeutic Monoclonal Antibodies
Top Cited Papers
- 1 August 2010
- journal article
- review article
- Published by Springer Science and Business Media LLC in Clinical Pharmacokinetics
- Vol. 49 (8), 493-507
- https://doi.org/10.2165/11531280-000000000-00000
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.Keywords
This publication has 109 references indexed in Scilit:
- Effect of plasma exchange in accelerating natalizumab clearance and restoring leukocyte functionNeurology, 2009
- Population Pharmacokinetics of Cetuximab in Patients With Squamous Cell Carcinoma of the Head and NeckThe Journal of Clinical Pharmacology, 2008
- Population pharmacokinetic data analysis of three phase I studies of matuzumab, a humanised anti-EGFR monoclonal antibody in clinical cancer developmentBritish Journal of Cancer, 2008
- Population pharmacokinetics–pharmacodynamics of alemtuzumab (Campath®) in patients with chronic lymphocytic leukaemia and its link to treatment responseBritish Journal of Clinical Pharmacology, 2007
- Decreased clinical response to infliximab in ankylosing spondylitis is correlated with anti-infliximab formationAnnals Of The Rheumatic Diseases, 2007
- A mechanism‐based binding model for the population pharmacokinetics and pharmacodynamics of omalizumabBritish Journal of Clinical Pharmacology, 2007
- Exposure-Effect Population Model of Inolimomab, a Monoclonal Antibody Administered in First-Line Treatment for Acute Graft-Versus-Host DiseaseClinical Pharmacokinetics, 2007
- Relationship between serum trough infliximab levels, pretreatment C reactive protein levels, and clinical response to infliximab treatment in patients with rheumatoid arthritisAnnals Of The Rheumatic Diseases, 2005
- TISSUE DISTRIBUTION AND RECEPTOR-MEDIATED CLEARANCE OF ANTI-CD11A ANTIBODY IN MICEPublished by American Society for Pharmacology & Experimental Therapeutics (ASPET) ,2005
- Production of recombinant protein therapeutics in cultivated mammalian cellsNature Biotechnology, 2004