Most drugs initiate their effects by binding to a drug target. The kinetics of binding have the potential to influence the utility of a drug. Physiology uses the magnitude of kinetic barriers to differentiate between reversible and irreversible states, leading to differentiated phenotypes. Under the appropriate circumstances the therapeutic index of some drugs is influenced by the kinetics and reversibility of a system. The ability for differentiated binding kinetics to define irreversible or reversible states and the impact of these differentiated states on a clinical outcome is proposed here to contribute to the magnitude of gastrointestinal toxicity observed with nonsteroidal anti-inflammatory agents (NSAIDs). This example and others highlight the potential for differentiated binding kinetics to provide clinical differentiation.
Keywords: Kinetics, Pharmacology, Cyclooxygenase, NSAID, GI toxicity, Irreversible
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