Pharmacokinetics interactions of monoclonal antibodies

[Display omitted] The clearance of therapeutic monoclonal antibodies (mAbs) typically does not involve cytochrome P450 (CYP450)-mediated metabolism or interaction with cell membrane transporters, therefore the pharmacokinetics interactions of mAbs and small molecule drugs are limited. However, a dru...

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Bibliographic Details
Published in:Pharmacological research 2016-09, Vol.111, p.592-599
Main Authors: Ferri, Nicola, Bellosta, Stefano, Baldessin, Ludovico, Boccia, Donatella, Racagni, Giorgi, Corsini, Alberto
Format: Article
Language:English
Subjects:
Alirocumab
Animals
Antibodies, Monoclonal - pharmacokinetics
Drug Interactions
Evolocumab
Humans
IL-6
Methotrexate
Monoclonal antibodies
PCSK9
Reticuloendothelial system
Simvastatin
Tocilizumab
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Summary:[Display omitted] The clearance of therapeutic monoclonal antibodies (mAbs) typically does not involve cytochrome P450 (CYP450)-mediated metabolism or interaction with cell membrane transporters, therefore the pharmacokinetics interactions of mAbs and small molecule drugs are limited. However, a drug may affect the clearance of mAbs through the modulation of immune response (e.g., methotrexate reduces the clearance of infliximab, adalimumab, and golimumab, possibly due to methotrexate⿿s inhibitory effect on the formation of antibodies against the mAbs). In addition, mAbs that are cytokine modulators may modify the metabolism of drugs through their effects on P450 enzymes expression. For example, cytokine modulators such as tocilizumab (anti-IL-6 receptor antibody) may reverse the ⿿inhibitory⿿ effect of IL-6 on CYP substrates, resulting in a ⿿normalization⿿ of CYP activities. Finally, a drug may alter the clearance of mAbs by either increasing or reducing the levels of expression of targets of mAbs on the cell surface. For instance, statins and fibrates induce PCSK9 expression and therefore increase cellular uptake and clearance of alirocumab and evolocumab, anti-PCSK9 antibodies. In the present review, we will provide an overview on the pharmacokinetics properties of mAbs as related to the most relevant examples of mAbs-small molecule drug interaction.
ISSN:1043-6618
1096-1186
DOI:10.1016/j.phrs.2016.07.015