Deuterated Drugs

Background

Deuterated compounds are transforming pharmaceutical development by replacing hydrogen (1H) with deuterium (2H), resulting in stronger carbon-deuterium bonds. This substitution enhances metabolic stability, prolongs drug half-life, and reduces dosing frequency, improving patient compliance.

By altering metabolic pathways, deuterated drugs can also lower toxic metabolite production, leading to safer therapeutic profiles. Additionally, these compounds allow for fine-tuning of pharmacokinetics and pharmacodynamics, enhancing selectivity and efficacy.

Deuterated compounds offer a novel, efficient approach to creating longer-lasting, safer, and more effective treatments, addressing key challenges in modern drug development.

Applications

In 2017, the US Food and Drug Administration (FDA) approved the first deuterated drug deutetrabenazine (Austedo) by Teva and became front runners deuterated pharmaceuticals. Currently there are over 19 drug candidates going through clinical trials. 

Deutetrabenazine is a selectively deuterated derivative of tetrabenazine, the active ingredient in Xenazine, which was approved in 2008 for treating Huntington’s disease-associated chorea. Compared to tetrabenazine, deutetrabenazine produces deuterated active metabolites with longer half-lives, enabling less frequent dosing.

The approval of Austedo, the deutetrabenazine-based drug, is noteworthy not only for demonstrating that deuterated drugs can secure FDA approval but also for its potential to inspire further innovations in drug development.

Deuterated drugs closely resemble their non-deuterated counterparts in terms of selectivity for biological receptors, resulting in nearly identical pharmacodynamic effects. However, the differences in metabolism between deuterated and non-deuterated forms are significant enough to have clinical relevance.

The primary objectives of drug deuteration include slowing the rate of metabolism to extend the drug's half-life, reducing the required dosage, and minimizing side effects.