2012
Rapid Evaluation in Whole Blood Culture of Regimens for XDR-TB Containing PNU-100480 (Sutezolid), TMC207, PA-824, SQ109, and Pyrazinamide
Wallis RS, Jakubiec W, Mitton-Fry M, Ladutko L, Campbell S, Paige D, Silvia A, Miller PF. Rapid Evaluation in Whole Blood Culture of Regimens for XDR-TB Containing PNU-100480 (Sutezolid), TMC207, PA-824, SQ109, and Pyrazinamide. PLOS ONE 2012, 7: e30479. PMID: 22279595, PMCID: PMC3261206, DOI: 10.1371/journal.pone.0030479.Peer-Reviewed Original ResearchMeSH KeywordsAdamantaneAntitubercular AgentsDiarylquinolinesDrug MonitoringDrug Therapy, CombinationEthylenediaminesExtensively Drug-Resistant TuberculosisHumansMicrobial Sensitivity TestsMycobacterium tuberculosisNitroimidazolesOxazolidinonesPyrazinamideQuinolinesReproducibility of ResultsTime FactorsConceptsPNU-100480Whole blood culturesPA-824Blood culturesWhole-blood bactericidal activityBactericidal activityStandard TB therapyDihydroxy vitamin DIntracellular M. tuberculosisBlood bactericidal activityCumulative activityPZA-resistant strainsHigh therapeutic concentrationsActive regimensTB regimensNew regimensTB therapyVitamin DOral dosingTherapeutic concentrationsDrug combinationsPharmacokinetic dataRegimensIndividual drugsTMC207SQ109 and PNU-100480 interact to kill Mycobacterium tuberculosis in vitro
Reddy VM, Dubuisson T, Einck L, Wallis RS, Jakubiec W, Ladukto L, Campbell S, Nacy CA. SQ109 and PNU-100480 interact to kill Mycobacterium tuberculosis in vitro. Journal Of Antimicrobial Chemotherapy 2012, 67: 1163-1166. PMID: 22258923, DOI: 10.1093/jac/dkr589.Peer-Reviewed Original ResearchMeSH KeywordsAdamantaneAnimalsAntitubercular AgentsCell LineDrug InteractionsEthylenediaminesMacrophagesMiceMicrobial ViabilityMycobacterium tuberculosisOxazolidinonesConceptsPNU-100480Whole blood culturesMycobacterium tuberculosisRate of killingBlood culturesOrder of efficacyChequerboard titrationIndividual drugsIntracellular M. tuberculosisIntracellular Mycobacterium tuberculosisTime-kill studiesTwo-drug interactionsIntracellular activityMtb killingJ774A.1 mouse macrophagesSQ109M. tuberculosisMajor metaboliteTuberculosisMouse macrophagesBactericidal activityDrugsEfficacyKillingMacrophages
2010
Biomarker-Assisted Dose Selection for Safety and Efficacy in Early Development of PNU-100480 for Tuberculosis
Wallis RS, Jakubiec W, Kumar V, Bedarida G, Silvia A, Paige D, Zhu T, Mitton-Fry M, Ladutko L, Campbell S, Miller PF. Biomarker-Assisted Dose Selection for Safety and Efficacy in Early Development of PNU-100480 for Tuberculosis. Antimicrobial Agents And Chemotherapy 2010, 55: 567-574. PMID: 21078950, PMCID: PMC3028776, DOI: 10.1128/aac.01179-10.Peer-Reviewed Original ResearchMeSH KeywordsAcetamidesAdolescentAdultAnimalsAntitubercular AgentsArea Under CurveDose-Response Relationship, DrugDrug Administration ScheduleHumansLinezolidMicrobial Sensitivity TestsMiddle AgedMycobacterium tuberculosisOxazolidinonesPyrazinamideRatsSerum Bactericidal TestTreatment OutcomeTuberculosisYoung AdultConceptsPNU-100480Whole-blood bactericidal activityMultiple ascending dosesDays of dosingSerious global health threatWhole blood culturesBactericidal activityGlobal health threatM. tuberculosis growthAscending dosesSixth cohortNew tuberculosis treatmentsPlasma drugTuberculosis treatmentPlasma concentrationsSafety signalsHealthy volunteersDose selectionRoutine safety testsNew treatmentsDay 27TuberculosisMycobacterium tuberculosisDosesHealth threatPharmacokinetics and Whole-Blood Bactericidal Activity against Mycobacterium tuberculosis of Single Doses of PNU-100480 in Healthy Volunteers
Wallis RS, Jakubiec WM, Kumar V, Silvia AM, Paige D, Dimitrova D, Li X, Ladutko L, Campbell S, Friedland G, Mitton-Fry M, Miller PF. Pharmacokinetics and Whole-Blood Bactericidal Activity against Mycobacterium tuberculosis of Single Doses of PNU-100480 in Healthy Volunteers. The Journal Of Infectious Diseases 2010, 202: 745-751. PMID: 20629533, DOI: 10.1086/655471.Peer-Reviewed Original ResearchConceptsWhole-blood bactericidal activityMean maximal concentrationPNU-100480Single dosesMinimum inhibitory concentrationHealthy volunteersBactericidal activityMycobacterium tuberculosisExperimental murine tuberculosisSingle ascending dosesSingle oral dosesDrug-resistant tuberculosisMaximal concentrationInhibitory concentrationAscending dosesMurine tuberculosisExposure of parentsOral dosesDaily dosesLog/dayLinezolidDrug concentrationsTuberculosisMycobactericidal activityDoses