Substitution of one or more hydrogen atoms with its heavy isotope deuterium, which is called deuteration, provides additional neutron to a molecule. Although it seems to be a subtle change, this structural modification, may improve the pharmacokinetic properties, efficacy and safety of drugs compared with the non-deuterated counterparts. The structural modification by incorporating deuterium into molecule and development of new drugs started since early 1960s, but the progress was slow. However, in the last two decades, deuteration process has been increasingly used to improve the pharmacokinetic characteristics of marketed drugs. In 2017, FDA approved the first deuterated drug, such as deutetrabenazine. Deuteration is used not only to improve the marketed drugs, but also to discover novel drugs. The FDA approved the pioneering de novo deuterated drug deucravacitinib in 2022.
Opportunities and challenges for deuteration
Deuteration provides the molecule with bond stability and doesn’t change steric hindrance or electronic properties. Deuterium might represent a safer bioisostere compared with fluorine, because fluorinated drugs may produce harmful species for both human health and the environment (e.g., fluoride or fluoroacetate). Deuterium (D) atoms have impact on absorption, distribution, metabolism, excretion and toxicity (ADMET) parameters.
Although the deuteration process has significant potential in the discovery of new drugs, it has some challenges as well. Deuteration technique is challenging, because this reaction needs a rate-limiting bond cleavage step. There are some other reasons which causes the drug failure of some deuterated analogues.
Reference
Di Martino, R.M.C., Maxwell, B.D., Pirali, T. 2023. Deuterium in drug discovery: progress, opportunities and challenges. Nat Rev Drug Discov (2023).
Billion doses antibiotic donation of Pfizer to eliminate trachoma, an eye disease causing blindness
Trachoma is an eye disease caused by the bacterium Chlamydia trachomatis. If it is not treated with antibiotics or a simple surgical procedure in time and properly, it may eventually result in blindness. It is a neglected tropical disease (NTD) all over the world, which may ultimately cause blindness of people.
Pfizer has partnered with International Trachoma Initiative (ITI) and delivered 1 billion doses of donated antibiotic. They started their donation program since 1998 to help treat and prevent trachoma across more than 40 countries as part of the World Health Organization (WHO) recommended S.A.F.E. strategy.
Source: World Health Organization. Trachoma. “Who Response.” https://www.who.int/news-room/fact sheets/detail/trachoma#:~:text=WHO%20adopted%20the%20SAFE%20strategy,Elimination%20of%20Trachoma%20by%202020.Last updated October 5, 2022. Accessed January 27, 2023.
