Optimizing Anti-mycobacterial Therapy Using A Pharmacology-based Approach
使用基于药理学的方法优化抗分枝杆菌治疗
基本信息
- 批准号:10540813
- 负责人:
- 金额:$ 19.87万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-12-15 至 2026-11-30
- 项目状态:未结题
- 来源:
- 关键词:Adverse eventAdvisory CommitteesAntibioticsAntimycobacterial AgentsAreaAzithromycinBronchiectasisCessation of lifeClinicalClinical InvestigatorClinical PharmacologyClinical TrialsCollaborationsColony-forming unitsCombined AntibioticsCombined Modality TherapyCommittee MembersCommunicable DiseasesCompanionsComplexCountryDataDevelopmentDiseaseDoseDrug ExposureDrug InteractionsDrug KineticsDrug resistanceDrug toxicityDrug usageEnzymesEvaluationFundingFutureGoalsHepatotoxicityImmune responseIncidenceInstitutionInvestigationKineticsKnowledgeLeadLearningLicensingLungLung diseasesMedicalMentored Patient-Oriented Research Career Development AwardMentorsMentorshipModelingMycobacterium InfectionsMycobacterium avium ComplexNew AgentsNitroimidazolesPathway interactionsPatientsPharmaceutical PreparationsPharmacodynamicsPharmacologyPharmacotherapyPhasePhysiciansPopulationPositioning AttributePravastatinPre-Clinical ModelResearchResearch PersonnelResourcesRifabutinRifampinScienceScientistSerumSputumTherapeuticTimeToxic effectTrainingTuberculosisWritinganalytical methodbactericidedesigndrug biological activitydrug developmentdrug-sensitivehigh riskimprovedin vivolung injuryminimal inhibitory concentrationmultidisciplinarymycobacterialnon-tuberculosis mycobacterianovelnovel therapeuticspharmacokinetic modelpharmacologicpharmacometricspredictive toolsresponsescreeningskill acquisitionskillsstandard carestandard of caresuccesstooltreatment effecttrial designtrial enrollmenttuberculosis drugstuberculosis treatment
项目摘要
Project Summary/Abstract
The global burden of mycobacterial infections remains staggering, with over 10 million new tuberculosis (TB)
cases and 1.2 million deaths in 2019, and a recent rising incidence of nontuberculous mycobacteria (NTM).
Treatment of both TB and NTM is hindered by the need for prolonged combination antibiotics, drug resistance,
toxicity, drug-drug interactions and sub-optimal efficacy. After decades without many new agents, there are
now concerted efforts to identify and integrate novel drugs, optimize existing drugs, and augment host immune
response. Clinical pharmacology, when integrated throughout drug development, defines critical relationships
between drug exposure and effect (or toxicity), identifies key interactions, and enhances treatment success.
However, to date, there is a dearth of physician scientists with dual training in infectious diseases and clinical
pharmacology who can champion these drug development efforts, especially for NTM.
In this proposal, the candidate will apply clinical pharmacology tools to the problem of mycobacterial
therapeutics and utilize the resources and framework of three funded clinical trials that are being led by
mentors and advisory committee members. Backed by a strong multidisciplinary advisory team with expertise
in clinical pharmacology, mycobacterial drug development, pharmacometrics, and mycobacteriology, the
candidate will 1) define the pharmacokinetics-pharmacodynamics (PK-PD) of azithromycin for Mycobacterium
avium complex (MAC) lung disease by applying the early bactericidal activity (EBA) trial design (Aim 1); 2)
identify predictors of toxicity for a novel nitroimidazole antibiotic using PK-toxicodynamic (PK-TD) modeling
(Aim 2); and 3) determine the magnitude of drug-drug interaction (DDI) between first-line TB treatment and
pravastatin as host-directed therapy (Aim 3). Each one of these aims will provide an opportunity to not only
learn but also implement pharmacologic analytical methods for the investigation of both TB and NTM. The
candidate will gain skills including population PK modeling, execution of early bactericidal activity trial design,
PK-toxicodynamic modeling, and development of a clinical toxicity prediction tool.
This K23 Mentored Patient-Oriented Research Career Development Award will serve not only to advance
research in mycobacterial therapeutics, but also support the candidate to gain the skills necessary to perform
fundamental and advanced clinical pharmacology analyses, lead clinical trials, and form strong multi-
institutional collaborations. Upon completion of this K23, the candidate will be well positioned as an
independent clinical investigator with expertise in infectious diseases, applied antimycobacterial pharmacology,
and NTM therapeutics.
Project Summary/Abstract
The global burden of mycobacterial infections remains staggering, with over 10 million new tuberculosis (TB)
cases and 1.2 million deaths in 2019, and a recent rising incidence of nontuberculous mycobacteria (NTM).
Treatment of both TB and NTM is hindered by the need for prolonged combination antibiotics, drug resistance,
toxicity, drug-drug interactions and sub-optimal efficacy. After decades without many new agents, there are
now concerted efforts to identify and integrate novel drugs, optimize existing drugs, and augment host immune
response. Clinical pharmacology, when integrated throughout drug development, defines critical relationships
between drug exposure and effect (or toxicity), identifies key interactions, and enhances treatment success.
However, to date, there is a dearth of physician scientists with dual training in infectious diseases and clinical
pharmacology who can champion these drug development efforts, especially for NTM.
In this proposal, the candidate will apply clinical pharmacology tools to the problem of mycobacterial
therapeutics and utilize the resources and framework of three funded clinical trials that are being led by
mentors and advisory committee members. Backed by a strong multidisciplinary advisory team with expertise
in clinical pharmacology, mycobacterial drug development, pharmacometrics, and mycobacteriology, the
candidate will 1) define the pharmacokinetics-pharmacodynamics (PK-PD) of azithromycin for Mycobacterium
avium complex (MAC) lung disease by applying the early bactericidal activity (EBA) trial design (Aim 1); 2)
identify predictors of toxicity for a novel nitroimidazole antibiotic using PK-toxicodynamic (PK-TD) modeling
(Aim 2); and 3) determine the magnitude of drug-drug interaction (DDI) between first-line TB treatment and
pravastatin as host-directed therapy (Aim 3). Each one of these aims will provide an opportunity to not only
learn but also implement pharmacologic analytical methods for the investigation of both TB and NTM. The
candidate will gain skills including population PK modeling, execution of early bactericidal activity trial design,
PK-toxicodynamic modeling, and development of a clinical toxicity prediction tool.
This K23 Mentored Patient-Oriented Research Career Development Award will serve not only to advance
research in mycobacterial therapeutics, but also support the candidate to gain the skills necessary to perform
fundamental and advanced clinical pharmacology analyses, lead clinical trials, and form strong multi-
institutional collaborations. Upon completion of this K23, the candidate will be well positioned as an
independent clinical investigator with expertise in infectious diseases, applied antimycobacterial pharmacology,
and NTM therapeutics.
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Elisa Helen Ignatius其他文献
Elisa Helen Ignatius的其他文献
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{{ truncateString('Elisa Helen Ignatius', 18)}}的其他基金
Optimizing Anti-mycobacterial Therapy Using A Pharmacology-based Approach
使用基于药理学的方法优化抗分枝杆菌治疗
- 批准号:
10371264 - 财政年份:2021
- 资助金额:
$ 19.87万 - 项目类别:
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