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 ResearchMeSH KeywordsAcetamidesAntitubercular AgentsDose-Response Relationship, DrugHumansLinezolidMycobacterium tuberculosisOxazolidinonesSerum Bactericidal TestTreatment OutcomeConceptsWhole-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