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Toward Consensus on Correct Interpretation of Protein Binding in Plasma and Other Biological Matrices for COVID‐19 Therapeutic Development
Author(s) -
Boffito Marta,
Back David J.,
Flexner Charles,
Sjö Peter,
Blaschke Terrence F.,
Horby Peter W.,
Cattaneo Dario,
Acosta Edward P.,
Anderson Peter,
Owen Andrew
Publication year - 2021
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.2099
Subject(s) - drug development , covid-19 , drug , intensive care medicine , drug discovery , antiviral drug , pharmacokinetics , pharmacodynamics , medicine , pharmacology , computational biology , virology , bioinformatics , biology , pathology , infectious disease (medical specialty) , disease
The urgent global public health need presented by severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) has brought scientists from diverse backgrounds together in an unprecedented international effort to rapidly identify interventions. There is a pressing need to apply clinical pharmacology principles and this has already been recognized by several other groups. However, one area that warrants additional specific consideration relates to plasma and tissue protein binding that broadly influences pharmacokinetics and pharmacodynamics. The principles of free drug theory have been forged and applied across drug development but are not currently being routinely applied for SARS‐CoV‐2 antiviral drugs. Consideration of protein binding is of critical importance to candidate selection but requires correct interpretation, in a drug‐specific manner, to avoid either underinterpretation or overinterpretation of its consequences. This paper represents a consensus from international researchers seeking to apply historical knowledge, which has underpinned highly successful antiviral drug development for other viruses, such as HIV and hepatitis C virus for decades.