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Drug-binding Cavities in Long-Lived Biologics: Cause for Concern but Also Potential Benefit

From Nikos Panayotatos Consulting, Orangeburg, New York.

Universally present but overlooked cavities or pockets in long-lived biopharmaceuticals, such as monoclonal antibodies (mAbs), are capable of binding small drugs. Such direct interactions can alter the pharmacokinetics of drugs and potentially affect clinical outcome. The extreme differences in the pharmacokinetic properties of these 2 classes of drugs largely account for such effects. This overlooked mechanism of biologic-chemical drug interaction should be considered before approval of new long-lived entities.

Key Words: Protein cavity • protein pocket • direct biologic–drug interactions • side effects • targeted drug delivery • drug binding • pharmacokinetics • slow release • monoclonal antibody (mAb)

Address for reprints: Nikos Panayotatos, PhD, Nikos Panayotatos Consulting, 95 Monmouth Court, Orangeburg, NY 10962; e-mail: nikospan{at}optonline.net.

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