3 research outputs found
Sticky & Dirty Proteins – or on the poorly characterised, peculiar, pharmacokinetic and immunostimulatory aspects of biopharmaceuticals
Biopharmaceuticals are among the most celebrated drugs.
However, despite decades of experience, our understanding of many in vivo
pharmacokinetic and adverse effects of biopharmaceuticals is still limited.
These include the delay in reaching the maximum plasma concentration for an
intravenously administered therapeutical protein, and the highly variable
plasma concentration during elimination of monoclonal antibodies. Both
observations can be explained by dynamical binding (‘stickiness’) of proteins
to various (bodily) surfaces.
Biopharmaceuticals also frequently contain (non-human) impurities, some of
which are harmful when administered (‘dirtiness’). This toxicity often is the
result of an intricate interplay of multiple cell types and effector pathways
which can be difficult to simulate in the laboratory. More sophisticated test
platforms are available, which can detect a number of untoward reactions that
would previously not have been discovered. However, no laboratory test is
fail-safe, and awareness of the possibility of adverse immunostimulation
caused by biopharmaceuticals is the most important aspect for early detection
and prevention of such cases in the future.
Centre for Human Drug Research (CHDR)LUMC / Geneeskund
Sticky & Dirty Proteins – or on the poorly characterised, peculiar, pharmacokinetic and immunostimulatory aspects of biopharmaceuticals
Biopharmaceuticals are among the most celebrated drugs.
However, despite decades of experience, our understanding of many in vivo
pharmacokinetic and adverse effects of biopharmaceuticals is still limited.
These include the delay in reaching the maximum plasma concentration for an
intravenously administered therapeutical protein, and the highly variable
plasma concentration during elimination of monoclonal antibodies. Both
observations can be explained by dynamical binding (‘stickiness’) of proteins
to various (bodily) surfaces.
Biopharmaceuticals also frequently contain (non-human) impurities, some of
which are harmful when administered (‘dirtiness’). This toxicity often is the
result of an intricate interplay of multiple cell types and effector pathways
which can be difficult to simulate in the laboratory. More sophisticated test
platforms are available, which can detect a number of untoward reactions that
would previously not have been discovered. However, no laboratory test is
fail-safe, and awareness of the possibility of adverse immunostimulation
caused by biopharmaceuticals is the most important aspect for early detection
and prevention of such cases in the future.
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