Heavy Metal

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The excellent drug development blog “In the pipeline” highlighted a fascinating phase 2 trial that is ongoing at the moment. Pentoxifylline is a methylxanthine phsophodiesterase inhibitor that has been used to treat peripheral vascular disease. It is also known to have anti-inflammatory properties and a recent Cochrane meta-analysis suggested that there may be a benefit in patients with diabetic nephropathy and albuminuria. The trial mentioned above is of an analog of one of the active metabolites of pentoxifylline called CTP-499. The clever thing about this molecule is that it is deuterated.

Deuterium is an isotope of hydrogen. Hydrogen typically has a single proton and no neutrons. Deuterium is a hydrogen atom with an added neutron. The thing that makes this interesting to drug companies is that it forms stronger bonds with other atoms than traditional hydrogen. As a result, liver enzymes take longer to break down a drug that has deuterium substituted for hydrogen and thus the half-life of a medication can theoretically be extended. There has been a rush recently to patent various drugs that have been “deuterated” although it is uncertain at this time whether or not this is going to be a successful strategy. There really are few safety concerns – the deuterated hydrogen would eventually form D2O or heavy water in the body prior to being excreted. Although too much heavy water would be deleterious, you would have to drink liters before you would see any adverse effects and the effect of these medications is likely to be minimal.

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