Drug-binding cavities in long-lived biologics: cause for concern but also potential benefit.
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.
Panayotatos
Nikos
N
Nikos Panayotatos Consulting, 95 Monmouth Court, Orangeburg, NY 10962, USA. nikospan@optonline.net
D000911:Antibodies, Monoclonal / Q000378:metabolism*; D001665:Binding Sites; D001688:Biological Products / Q000378:metabolism*; D016503:Drug Delivery Systems; D015195:Drug Design; D004347:Drug Interactions; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D001688:Biological Products; D004364:Pharmaceutical Preparations; D011506:Proteins