Delamanid, a new 6-nitro-2, 3-dihydroimidazo[2, 1-b]oxazole for the management of tuberculosis resistant to at least isoniazid and rifampicin. (January 2014)

• Record Type: Journal Article
• Authors: Diacon, Andreas H; von Groote-Bidlingmaier, Florian; Donald, Peter R
• Is Part Of: Expert opinion on orphan drugs. Volume 2:Number 1(2014:Jan.)
• Page Start: 87
• Page End: 94
• Publication Date: 2014-01
• Subjects: Orphan drugs -- Periodicals; Rare diseases -- Periodicals; Chemotherapy -- Periodicals; 615.1
• DOI: 10.1517/21678707.2014.863729
• Languages: English
• ISSNs: 2167-8707

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p> <bold> <italic>Introduction:</italic> </bold> Novel therapeutic agents are urgently needed to combat drug-resistant tuberculosis. <ext-link ext-link-type="uri" xlink:href="http://informahealthcare.com/action/doSearch?type=advanced&displaySummary=true&displaySummary=true&field1=keywords&text1=Delamanid&logicalOpe1=OR&field2=articletitle&text2=Delamanid&logicalOpe2=AND&field3=all&text3=&search=Search&categoryId=41010274&categoryId=40002416&categoryId=40004717&categoryId=40004717&filter=multiple&AfterMonth=1&AfterYear=&BeforeMonth=12&BeforeYear=&sortBy=date&nh=20" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">Delamanid</ext-link> is a new 6-nitro-2, 3-dihydroimidazo[2, 1-b]oxazole developed from a new chemical group to which no resistance exists. Preclinical experience found delamanid efficacious with a good safety profile except for QT prolongation; <italic>in vitro</italic> no interaction, inhibitory nor stimulatory with human and animal liver microsomes or a range of CYP enzymes have been demonstrated; interactions with antiretroviral agents are unlikely but this must still be demonstrated in clinical trials. A dose-ranging early bactericidal activity study provided proof of concept, and a controlled trial over the first 8 weeks of multidrug-resistant tuberculosis treatment found accelerated sputum culture negativity. Delamanid is in ongoing clinical trials in children, adults and HIV-infected adults receiving antiretroviral treatment.</p> <p> <bold> <italic>Areas covered:</italic> </bold> Using keywords, such as imidazooxazole, nitroimidazoles, OPC-67683, delamanid and antituberculosis drugs, the literature concerning the development and assessment, both <italic>in vitro</italic> and <italic>in vivo, </italic> of a new antituberculosis drug, delamanid was reviewed.</p> <p> <bold> <italic>Expert opinion:</italic> </bold> In view of efficacy, absence of major toxicity thus far and probable lack of interaction with antiretroviral agents, delamanid is a potential addition to the therapeutic armamentarium for tuberculosis.</p> </abstract>