Early bactericidal activity of delamanid (OPC-67683) in smear-positive pulmonary tuberculosis patients

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dc.contributor.authorDiacon A.H.
dc.contributor.authorDawson R.
dc.contributor.authorHanekom M.
dc.contributor.authorNarunsky K.
dc.contributor.authorVenter A.
dc.contributor.authorHittel N.
dc.contributor.authorGeiter L.J.
dc.contributor.authorWells C.D.
dc.contributor.authorPaccaly A.J.
dc.contributor.authorDonald P.R.
dc.date.accessioned2011-10-13T16:58:39Z
dc.date.available2011-10-13T16:58:39Z
dc.date.issued2011
dc.description.abstractBACKGROUND: Delamanid (OPC-67683) is a novel mycolic acid biosynthesis inhibitor active against Mycobacterium tuberculosis at a low minimum inhibitory concentration. METHODS: Forty-eight patients with smear-positive tuberculosis (63% male; 54.7 ± 9.9 kg; 30.7 ± 10.8 years) were randomly assigned to receive delamanid 100, 200, 300 or 400 mg daily for 14 days. Colony forming units (cfu) of M. tuberculosis were counted on agar plates from overnight sputum collections to calculate early bactericidal activity (EBA), defined as fall in log10 cfu/ml sputum/day. RESULTS: The EBA of delamanid was monophasic and not significantly different between dosages; however, more patients receiving 200 mg (70%) and 300 mg (80%) experienced a response of ≥0.9 log10 cfu/ml sputum decline over 14 days than those receiving 100 mg (45%) and 400 mg (27%). The average EBA of all dosages combined (0.040 ± 0.056 log10 cfu/ml sputum/day) was significant from day 2 onward. Delamanid exposure was less than dosage-proportional, reaching a plateau at 300 mg, likely due to dose-limited absorption. Moderate but significant correlation was found between Cmax and EBA, indicating exposure dependence. Delamanid was well tolerated without significant toxicity. CONCLUSIONS: Delamanid at all dosages was safe, well tolerated and demonstrated significant exposure-dependent EBA over 14 days, supporting further investigation of its pharmacokinetics and anti-tuberculosis activity. © 2011 The Union.
dc.description.versionArticle
dc.identifier.citationInternational Journal of Tuberculosis and Lung Disease
dc.identifier.citation15
dc.identifier.citation7
dc.identifier.citationhttp://www.scopus.com/inward/record.url?eid=2-s2.0-79958718650&partnerID=40&md5=388b1a3707101652d141de89678b7846
dc.identifier.issn10273719
dc.identifier.other10.5588/ijtld.10.0616
dc.identifier.urihttp://hdl.handle.net/10019.1/16806
dc.subjectDelamanid
dc.subjectEarly bactericidal activity
dc.subjectOPC-67683
dc.subjectTuberculosis
dc.subjectdelamanid
dc.subjectadult
dc.subjectarticle
dc.subjectbactericidal activity
dc.subjectclinical article
dc.subjectcontrolled study
dc.subjectdose response
dc.subjectdrug absorption
dc.subjectdrug blood level
dc.subjectdrug dose comparison
dc.subjectdrug efficacy
dc.subjectdrug exposure
dc.subjectdrug fatality
dc.subjectdrug tolerability
dc.subjectfemale
dc.subjecthuman
dc.subjectlung tuberculosis
dc.subjectmale
dc.subjectmaximum plasma concentration
dc.subjectmorning dosage
dc.subjectmulticenter study
dc.subjectphase 2 clinical trial
dc.subjectpriority journal
dc.subjectQT prolongation
dc.subjectrandomized controlled trial
dc.subjectsputum smear
dc.titleEarly bactericidal activity of delamanid (OPC-67683) in smear-positive pulmonary tuberculosis patients
dc.typeArticle
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