Deuterated Active Pharmaceutical Ingredients in Drugs

Deuterium is the non-radioactive, naturally occurring relative of hydrogen. Deuterium Labeled Active Pharmaceutical Ingredients (D-APIs) are currently undergoing multiple clinical trials in order to investigate improved metabolic profile, higher oral bioavailability and lower dosages compared to their conventional API counterparts. Replacement of hydrogen with deuterium at distinct sites of the physiological active substance may alter some properties of a drug. The deuterium switch will not change the interaction between the molecule and its biological target which is relevant for the efficacy of the drug. However, due to the strength of the deuterium carbon bond compared to the carbon hydrogen bond, the pharmacological pathway and the degradation of the D-API once bound to the biological target can be significantly impacted. This may reduce or even eliminate negative side effects, undesired properties, or toxicity of the drug while maintaining its efficacy. The first deuterated drug that received regulatory approval was Deutetrabenazine (Austedo) from Teva in 2017.