A New Paradigm for Drug Deuteration Based on Computed Binding Isotope Effects

Deuterated drugs offer longer action and lower market introduction costs. The current motivation for drug deuteration is primarily to slow metabolic processes. An alternative paradigm is proposed using binding isotope effects to minimize deuterium release, reduce peak drug concentrations linked to side effects, and extend the duration of the drug's active form. Identifying nonexchangeable hydrogen atoms with binding isotope effects less than unity through theoretical calculations is essential for this approach.