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Farmacokinetiek van monoklonale antilichamen

Translated title of the contribution: The pharmacokinetics of monoclonal antibodies
  • R. J. Keizer
  • , A. D.R. Huitema
  • , C. W.N. Damen
  • , J. H.M. Schellens
  • , J. H. Beijnen

Research output: Contribution to journalReview articlepeer-review

2 Citations (Scopus)

Abstract

- Monoclonal antibodies (MOABs) are, due to their specificity, increasingly being deployed for therapeutic purposes. - MOABs are derived from immunoglobulins and are fully or partially of murine or human origin. They are administered parenterally: mostly intravenously, but subcutaneous or intramuscular administration is also possible, in which case absorption probably occurs through the lymphatic system. - The distribution of MOABs from the bloodstream into the tissues is slow and is hampered by the high molecular size of the MOABs, which is a lesser problem for fragments of antibodies (Fab fragments). - MOABs are metabolised to peptides and amino acids. This process takes place in many tissues of the body, but probably predominantly in epithelial cells. - As a consequence of the saturable binding of the MOAB to its target, a dose-dependent (non-linear) elimination is often observed. - Immune reactions can accelerate the elimination of antibodies, partially depending on the degree of humanisation of the antibody. - Antibodies and endogenous immunoglobulins are protected from elimination by binding to protective receptors (neonatal Fc-receptor; FcRn), which explains their long half-lives (up to 4 weeks). - Metabolic pharmacokinetic interactions with other drugs have not been reported and are not expected. - It is expected that in the years to come, new MOABs directed towards new targets will appear on the market, as well as existing antibodies with improved pharmacokinetic properties.

Translated title of the contributionThe pharmacokinetics of monoclonal antibodies
Original languageDutch
Pages (from-to)683-688
Number of pages6
JournalNederlands Tijdschrift voor Geneeskunde
Volume151
Issue number12
Publication statusPublished - 24 Mar 2007
Externally publishedYes

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