Several monoclonal antibodies (mAbs) (omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab) are currently approved for the treatment of severe asthma. They have complex pharmacokinetic profiles. These profiles are unique in that they are dependent on their structure as well as can be markedly influenced by the biology of their target antigen, but their general behaviour can still be considered a class property, similar to their endogenous IgG counterpart. They cannot be administered by oral route, have a slow distribution into tissue, are metabolized to peptides and amino acids in several tissues but are protected from degradation by binding to protective receptors (the FcRn), which explains their long elimination half-lives. Their clearance is nonlinear because of the saturation of the target-mediated elimination. Also anti-drug antibody (ADA) response and off-target binding, as well as their glycosylation pattern, can influence the pharmacokinetics of mAbs.

Monoclonal antibodies for severe asthma: Pharmacokinetic profiles / Matera, M. G.; Calzetta, L.; Rogliani, P.; Cazzola, M.. - In: RESPIRATORY MEDICINE. - ISSN 0954-6111. - 153(2019), pp. 3-13. [10.1016/j.rmed.2019.05.005]

Monoclonal antibodies for severe asthma: Pharmacokinetic profiles

Calzetta L.;
2019

Abstract

Several monoclonal antibodies (mAbs) (omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab) are currently approved for the treatment of severe asthma. They have complex pharmacokinetic profiles. These profiles are unique in that they are dependent on their structure as well as can be markedly influenced by the biology of their target antigen, but their general behaviour can still be considered a class property, similar to their endogenous IgG counterpart. They cannot be administered by oral route, have a slow distribution into tissue, are metabolized to peptides and amino acids in several tissues but are protected from degradation by binding to protective receptors (the FcRn), which explains their long elimination half-lives. Their clearance is nonlinear because of the saturation of the target-mediated elimination. Also anti-drug antibody (ADA) response and off-target binding, as well as their glycosylation pattern, can influence the pharmacokinetics of mAbs.
Monoclonal antibodies for severe asthma: Pharmacokinetic profiles / Matera, M. G.; Calzetta, L.; Rogliani, P.; Cazzola, M.. - In: RESPIRATORY MEDICINE. - ISSN 0954-6111. - 153(2019), pp. 3-13. [10.1016/j.rmed.2019.05.005]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2902004
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