Is Delamanid suitable for patients with multidrug-resistant tuberculosis in all age groups?

Delamanid(Delamanid)also known asOPC-67683, is developed by Japan's Otsuka Pharmaceutical Co., Ltd.. Delamanid is used to treat multidrug-resistant tuberculosis in adults (≥18 years old). Delamani is under marketing review for multidrug-resistant tuberculosis in Japan, the first drug application submitted for this indication in Japan. Delamani has received orphan drug status in the EU and Japan.

Delamaniis highly bound to all plasma proteins, with a binding rate to total protein≥99.5%. Delamanid is metabolized primarily by albumin and to a lesser extentCYP3A4. The metabolism of delamanid may also be regulated, to a lesser extent, by the liver CYP1A1, CYP2D6 and CYP2E1. Four major metabolites (M1-M4) were found in the plasma of patients treated with delamanid, with M1 and M3 accounting for 13% of total human plasma exposure - 18%. Although they retain no significant pharmacological activity, they may still cause prolongation of the QT interval. This is especially true for the major metabolite of M1 (DM-6705), delamanid.

Delamanid is mainly metabolized by serum albumin via 6-nitro-2, 3-Dihydroimidazo[2,1-b]Hydrolytic cleavage of the azole moiety forms M1 (DM-6705). The formation of this major metabolite is thought to be the key starting point for the delamanidmetabolic pathway. M1 (DM-6705)can be further catalyzed through three pathways. In the first metabolic pathway, DM-6705 undergoes hydroxylation of the oxazole moiety to form M2 ((4RS,5S)-DM-6720), followed by CYP3A4-mediated hydroxyl oxidation and tautomerization of the oxazole to form the iminoketone metabolite M3 ((S)-DM-6718)4. The second metabolic pathway involves hydrolysis and deamination of azolamine to form M4 (DM-6704), followed by hydroxylation to M6 ((4R, 5S)-DM-6721) and M7 ((4S, 5S)-DM-6722), the azole is oxidized to another ketone metabolite M8 ((S)-DM-6717)4. The third pathway involves hydrolytic cleavage of the azole ring to form M5 (DM-6706). If you want to get more high-quality information, you can contact Yaode, and Yaode will do its best to learn more about high-quality overseas drugs for you.

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