Pretomanid-D5

Pretomanid-D5 is a deuterated version of pretomanid, an anti-tuberculosis drug that was recently approved by the US Food and Drug Administration (FDA) for the treatment of drug-resistant tuberculosis. Pretomanid-D5 is a stable isotope-labeled analogue of pretomanid, which means that it contains five deuterium atoms in place of hydrogen atoms at specific positions in the molecule. This modification does not affect the pharmacological activity of the drug, but it allows for more accurate measurements of its pharmacokinetics and metabolism in clinical studies. Pretomanid-D5 is typically administered orally in combination with other anti-tuberculosis drugs, such as bedaquiline and linezolid, to treat multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). The drug works by inhibiting the synthesis of mycolic acids, which are essential components of the bacterial cell wall in Mycobacterium tuberculosis, the causative agent of tuberculosis. By disrupting the integrity of the cell wall, pretomanid-D5 and its co-administered drugs can effectively kill the bacteria and prevent the spread of the disease. The chemical formula of pretomanid-D5 is C19H17D5N4O2, and its molecular weight is 332.43 g/mol. The drug has a half-life of approximately 11 hours, and it is primarily metabolized by the liver through the cytochrome P450 system. The main metabolite of pretomanid-D5 is a hydroxylated derivative, which is also labeled with deuterium atoms. The drug has moderate to high protein binding (>99%) and is excreted mainly in the feces (64%) and to a lesser extent in the urine (36%). Pretomanid-D5 has been shown to be safe and well-tolerated in clinical trials, with a low incidence of adverse effects such as nausea, diarrhea, and headache.