Pharmacokinetics of Anti-tuberculosis and Antiretroviral Drugs in Children
儿童抗结核和抗逆转录病毒药物的药代动力学
基本信息
- 批准号:8508996
- 负责人:
- 金额:$ 53.84万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-07-15 至 2017-04-30
- 项目状态:已结题
- 来源:
- 关键词:15 year old3 year oldAdultAffectAfricaAfrica South of the SaharaAfricanAgeAm 80Anti-Retroviral AgentsAntitubercular AgentsCYP3A4 geneCessation of lifeChildChildhoodDataDeath RateDiseaseDoseDrug FormulationsDrug InteractionsDrug KineticsEnzymesEpidemicEthambutolFrequenciesGenetic PolymorphismGhanaGoalsHIVInfectionInterdisciplinary StudyLeadNevirapinePharmaceutical PreparationsPharmacologyPlasmaPositioning AttributePrincipal InvestigatorPublic HealthPublishingPyrazinamideRecommendationRegimenResearchResourcesRifampinRiskSafetyTechnology TransferTestingTherapeuticTuberculosisWeightWorld Health Organizationabsorptionage groupagedbaseclinical caredevelopmental geneticsdosagedrug clearancedrug metabolismefavirenzeffective therapyenzyme activityexperiencehigh riskinnovationinsightisoniazidnon-nucleoside reverse transcriptase inhibitorspillprogramstuberculosis drugstuberculosis treatment
项目摘要
DESCRIPTION (provided by applicant): Tuberculosis (TB) in children is a major global public health challenge. It is estimated that about 15 -20% of the global TB caseload occur in children < 15 years old. Children are also highly susceptible to the dual epidemics of human immunodeficiency virus (HIV) and TB. HIV-infected children are at a higher risk of developing active TB and TB-related death. The treatment of TB, as well as TB/HIV coinfection in children is complicated by poor drug absorption, drug-drug interactions, high pill burden and lack of appropriate formulations. In addition, dosage recommendations for children are often extrapolated from pharmacokinetic (PK) studies in adults. Consequently, the recommended dosages of the anti-TB and antiretroviral medications have been associated with a high frequency of sub-therapeutic plasma concentrations. The lack of pediatric PK data for commonly prescribed medications in children with TB and TB/HIV coinfection represents a major obstacle to the safe and effective treatment of these conditions in children. Our long-term goal is to develop a multidisciplinary research program to study the PK of available and new anti-TB and anti-HIV medications in children in sub-Saharan Africa. The objective of this proposal is to determine the PK of the first-line anti-TB and anti-HIV drugs, as well as characterize the factors associated with variable PK and drug-drug interactions in children in Ghana, West Africa. Our overarching hypothesis is that previous studies have underestimated the effect of developmental and genetic differences in drug metabolism, drug-drug interactions, as well as the risk for suboptimal drug concentrations in children. Our hypotheses will be pursued through three specific aims. Aim 1 will determine whether the WHO recommended increased dosages of isoniazid, rifampin, pyrazinamide and ethambutol administered to African children with active TB infection (with or without HIV co- infection) achieve adult-equivalent therapeutic drug concentrations, and identify possible predictors of sub- therapeutic concentrations. Aim 2 will determine whether rifampin-containing TB therapy induces drug clearance substantially in young TB/HIV co-infected children resulting in reduced nevirapine exposure as compared to children receiving nevirapine therapy without anti-TB therapy. Aim 3 will determine whether rifampin-containing TB therapy significantly influence efavirenz concentrations in older TB/HIV co-infected children compared to HIV-infected children treated with a similar regimen in the absence of anti-TB treatment. Successful completion of the proposed studies will generate fundamental PK data for these commonly prescribed medications, as well as provide insights into predictors of the variable PK in children. Without such data, rational decisions about prescribing anti-TB and anti-HIV medications in children are not possible. PHS 398/2590 (Rev. 11/07) Page Continuation Format Page
描述(申请人提供):儿童结核病是一项重大的全球公共卫生挑战。据估计,全球约15%-20%的结核病病例发生在15岁的儿童中。儿童也极易受到人类免疫缺陷病毒(艾滋病毒)和结核病的双重流行。感染艾滋病毒的儿童患活动性结核病和结核病相关死亡的风险更高。结核病以及儿童结核病/艾滋病毒混合感染的治疗因药物吸收不良、药物-药物相互作用、高药丸负担和缺乏适当配方而变得复杂。此外,儿童的剂量推荐通常是从成人的药代动力学(PK)研究推断出来的。因此,抗结核和抗逆转录病毒药物的推荐剂量与亚治疗性血浆浓度的高频率相关。患有结核病和结核病/艾滋病毒混合感染的儿童缺乏常用处方药的儿科PK数据,这是安全和有效治疗儿童这些疾病的主要障碍。我们的长期目标是开发一项多学科研究计划,以研究撒哈拉以南非洲儿童现有的和新的抗结核病和抗艾滋病毒药物的PK。这项建议的目的是确定一线抗结核病和抗艾滋病毒药物的PK,以及表征与西非加纳儿童的可变PK和药物-药物相互作用相关的因素。我们的主要假设是,以前的研究低估了发育和遗传差异对药物代谢、药物-药物相互作用的影响,以及儿童药物浓度低于最佳水平的风险。我们的假设将通过三个具体目标来实现。目的1将确定世界卫生组织建议增加非洲活动性结核病感染儿童(合并或不合并艾滋病毒感染)的异烟肼、利福平、吡津酰胺和乙胺丁醇的剂量是否达到成人同等的治疗药物浓度,并确定亚治疗浓度的可能预测因素。目的2将确定与接受奈韦拉平治疗但未接受抗结核治疗的儿童相比,含有利福平的结核病治疗是否能在很大程度上促进合并感染结核病的儿童的药物清除,从而减少奈韦拉平的暴露。目的3将确定在没有抗结核治疗的情况下,与接受类似方案治疗的艾滋病毒感染儿童相比,含有利福平的结核病治疗是否显著影响合并感染结核病/艾滋病毒的老年儿童的依法韦仑浓度。这些拟议研究的成功完成将产生这些常用处方药的基本PK数据,并为儿童变量PK的预测因素提供洞察力。没有这样的数据,就不可能做出合理的决定,为儿童开出抗结核病和抗艾滋病毒的药物。PHS 398/2590(11/07版)页面续格式页面
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Awewura Jacob Kwara其他文献
Awewura Jacob Kwara的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Awewura Jacob Kwara', 18)}}的其他基金
Pharmacokinetics and Pharmacodynamics of Dolutegravir in Children Weighing ≥20 Kg Living with HIV with and without TB Coinfection
多替拉韦在体重≤20公斤的HIV感染者合并或未合并结核感染的儿童中的药代动力学和药效学
- 批准号:
10175510 - 财政年份:2020
- 资助金额:
$ 53.84万 - 项目类别:
Pharmacokinetics and Pharmacodynamics of Dolutegravir in Children Weighing ≥20 Kg Living with HIV with and without TB Coinfection
多替拉韦在体重≤20公斤的HIV感染者合并或未合并结核感染的儿童中的药代动力学和药效学
- 批准号:
10311554 - 财政年份:2020
- 资助金额:
$ 53.84万 - 项目类别:
Training Program in Tuberculosis and HIV Research in Ghana
加纳结核病和艾滋病毒研究培训计划
- 批准号:
9324379 - 财政年份:2016
- 资助金额:
$ 53.84万 - 项目类别:
Pharmacokinetics of Anti-tuberculosis and Antiretroviral Drugs in Children
儿童抗结核和抗逆转录病毒药物的药代动力学
- 批准号:
10470380 - 财政年份:2012
- 资助金额:
$ 53.84万 - 项目类别:
Pharmacokinetics of Anti-tuberculosis and Antiretroviral Drugs in Children
儿童抗结核和抗逆转录病毒药物的药代动力学
- 批准号:
9052788 - 财政年份:2012
- 资助金额:
$ 53.84万 - 项目类别:
Pharmacokinetics of Anti-tuberculosis and Antiretroviral Drugs in Children
儿童抗结核和抗逆转录病毒药物的药代动力学
- 批准号:
8402238 - 财政年份:2012
- 资助金额:
$ 53.84万 - 项目类别:
Pharmacokinetics of Anti-tuberculosis and Antiretroviral Drugs in Children
儿童抗结核和抗逆转录病毒药物的药代动力学
- 批准号:
8658450 - 财政年份:2012
- 资助金额:
$ 53.84万 - 项目类别:
Pharmacokinetics of Anti-tuberculosis and Antiretroviral Drugs in Children
儿童抗结核和抗逆转录病毒药物的药代动力学
- 批准号:
9769798 - 财政年份:2012
- 资助金额:
$ 53.84万 - 项目类别:
Pharmacokinetics of Anti-tuberculosis and Antiretroviral Drugs in Children
儿童抗结核和抗逆转录病毒药物的药代动力学
- 批准号:
10241940 - 财政年份:2012
- 资助金额:
$ 53.84万 - 项目类别:
Pharmacokinetics of Anti-tuberculosis and Antiretroviral Drugs in Children
儿童抗结核和抗逆转录病毒药物的药代动力学
- 批准号:
9319908 - 财政年份:2012
- 资助金额:
$ 53.84万 - 项目类别:
相似海外基金
Development and social implementation of unified developmental screening for health checkups for 3-year-old children in local governments
地方政府统一开展3岁儿童健康检查发育筛查工作的开展及社会实施
- 批准号:
23H01039 - 财政年份:2023
- 资助金额:
$ 53.84万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Low vision screening at 3-year-old children's health check-ups: development of a simple and accurate visual acuity testing software
3岁儿童体检中的低视力筛查:开发简单准确的视力测试软件
- 批准号:
23K02283 - 财政年份:2023
- 资助金额:
$ 53.84万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
0-3-year-old children's language and literacy learning at home in a digital age (0-3s, Tech and Talk)
数字时代0-3岁儿童在家学习语言和识字(0-3s,Tech and Talk)
- 批准号:
ES/W001020/1 - 财政年份:2022
- 资助金额:
$ 53.84万 - 项目类别:
Research Grant
Associations between physical activity levels of mothers and their 1-3 year old children: examining maternal self-efficacy as a mediator
母亲和 1-3 岁孩子体力活动水平之间的关联:检查作为中介的母亲自我效能感
- 批准号:
324339 - 财政年份:2015
- 资助金额:
$ 53.84万 - 项目类别:
Lived time of 3-year-old children in early childhood education and care: Reconsidering continuity of life and development
3岁儿童在幼儿教育和保育中的生存时间:重新思考生命和发展的连续性
- 批准号:
15K17356 - 财政年份:2015
- 资助金额:
$ 53.84万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Development of family support program to form healthy 3-year-old children and their mothers
制定家庭支持计划,培养健康的3岁儿童及其母亲
- 批准号:
24593457 - 财政年份:2012
- 资助金额:
$ 53.84万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
SUPPORTING 2 AND 3 YEAR OLD PRE-KINDERGARTEN READINESS
支持 2 岁和 3 岁儿童做好学前准备
- 批准号:
7699693 - 财政年份:2008
- 资助金额:
$ 53.84万 - 项目类别:
ADENOIDECTOMY FOR OTITIS MEDIA IN 2/3 YEAR OLD CHILDREN
2/3 岁儿童中耳炎的腺切除术
- 批准号:
6350559 - 财政年份:1997
- 资助金额:
$ 53.84万 - 项目类别:
EMOTIONAL AND BEHAVIOR PROBLEMS IN 1-3 YEAR OLD CHILDREN
1-3 岁儿童的情绪和行为问题
- 批准号:
2890762 - 财政年份:1997
- 资助金额:
$ 53.84万 - 项目类别:
EMOTIONAL AND BEHAVIOR PROBLEMS IN 1-3 YEAR OLD CHILDREN
1-3 岁儿童的情绪和行为问题
- 批准号:
2841735 - 财政年份:1997
- 资助金额:
$ 53.84万 - 项目类别: