Overcoming Tramadol Resistance In CYP2D6 Poor Metabolizers
克服 CYP2D6 代谢不良者的曲马多耐药性
基本信息
- 批准号:8713969
- 负责人:
- 金额:$ 58.31万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-02-01 至 2016-07-31
- 项目状态:已结题
- 来源:
- 关键词:Absence of pain sensationAdoptedAnalgesicsBindingCaucasiansCaucasoid RaceClinical TrialsControlled Clinical TrialsCountryCross-Over StudiesCyclic GMPCytochrome P-450 CYP2D6DataDoseDrug FormulationsElementsFundingGeneric DrugsGenetic Crossing OverGenotypeHumanIndividualIsoenzymesMarketingMetabolicModelingNociceptive StimulusOpiate AddictionOpioidOpioid ReceptorParentsPatientsPharmaceutical PreparationsPhasePhase I Clinical TrialsPhenotypePhysiciansPlaguePopulationProductionRandomizedResistanceRiskSalesSerumSmall Business Innovation Research GrantSpinalTabletsTestingTramadolbaseimprovednovelnovel therapeuticspilot trialpublic health relevanceresearch clinical testing
项目摘要
DESCRIPTION (provided by applicant): Tramadol is a widely prescribed analgesic, with over 25 million prescriptions and $565 million in retail sales in 2009, making it among the best selling
generic drugs. One of the advantages of tramadol over traditional opioids is its lower risk of opioid dependence, resulting in it having an unscheduled status in the U.S. and other countries. Although its mode of action is not completely understood, its analgesic activity is due to synergy between both the parent drug and the desmethyltramadol (M1) metabolite. The production of M1 and its opioid activity is critically dependent on the polymorphic isoenzyme of the debrisoquine-type, cytochrome P450 2D6 (CYP2D6). Approximately 10% of Caucasians have a genotype that results in reduced activity of CYP2D6. These individuals are poor metabolizers (PM) of tramadol, and their M1 serum concentration is significantly less than normal subjects. Several well controlled clinical trials have shown that the analgesic effect of tramadol is decreased or absent in PM subjects who have low CYP2D6 enzymatic activity. The impact of tramadol resistance in 10% of the U.S. population with low or absent CYP2D6 activity is significant, with upwards of a million patients receiving inadequate analgesia from tramadol therapy annually. Further, the need to switch nonresponders to traditional opioids increases their risk of opioid dependence. Within this need- analysis, there exists an opportunity to develop an "improved tramadol" that would be effective in all patients. Such a product would be expected to be quickly adopted by the market and displace existing tramadol sales. Based on extensive single-dose/steady-state human pilot data gathered in the SBIR Phase I segment, we identified a new proprietary M1/Tramadol tablet (SR105) that we hypothesize will overcome tramadol resistance in PMs by directly supplementing these patients with the M1 metabolite that they are incapable of generating on their own. By providing both the M1 metabolite and the parent drug, the entire spectrum of opioid and monoaminergic activity will be restored in subjects with the PM phenotype. This SBIR Phase II proposal aims to develop and finalize the required elements to open an IND with the FDA and to conduct a phase 1, two-segment, randomized cross-over clinical trial in 60 subjects that will begin to test our hypothesis.
描述(由申请人提供):曲马多是一种广泛使用的镇痛药,2009年有超过2500万张处方和5.65亿美元的零售额,是最畅销的药物之一
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 }}
STUART J KAHN其他文献
STUART J KAHN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('STUART J KAHN', 18)}}的其他基金
A Phase 1 Randomized Single Oral Dose Four Period Cross-Over Study Investigating Omnitram Dose Proportionality and Food Effect in Normal Human Subjects
一项 1 期随机单次口服剂量四期交叉研究,调查 Omnitram 剂量比例和食物对正常人类受试者的影响
- 批准号:
10372803 - 财政年份:2019
- 资助金额:
$ 58.31万 - 项目类别:
A Phase 1 Randomized Single Oral Dose Four Period Cross-Over Study Investigating Omnitram Dose Proportionality and Food Effect in Normal Human Subjects
一项 1 期随机单次口服剂量四期交叉研究,调查 Omnitram 剂量比例和食物对正常人类受试者的影响
- 批准号:
10029002 - 财政年份:2019
- 资助金额:
$ 58.31万 - 项目类别:
HLS- A Phase 1 Open-Label Dose-Escalation with Expansion Study of SX-682 in MDS Patients
HLS-SX-682 在 MDS 患者中的 1 期开放标签剂量递增和扩展研究
- 批准号:
9789451 - 财政年份:2018
- 资助金额:
$ 58.31万 - 项目类别:
A Phase 1 Clinical Trial Evaluating the Novel Small Molecule Immuno-Oncology Antagonist SX-682 Alone and With Pembrolizumab in Metastatic Melanoma
评估新型小分子免疫肿瘤拮抗剂 SX-682 单独使用以及与 Pembrolizumab 联合治疗转移性黑色素瘤的 1 期临床试验
- 批准号:
9348033 - 财政年份:2017
- 资助金额:
$ 58.31万 - 项目类别:
A Phase 1 Clinical Trial Evaluating the Novel Small Molecule Immuno-Oncology Antagonist SX-682 Alone and With Pembrolizumab in Metastatic Melanoma
评估新型小分子免疫肿瘤拮抗剂 SX-682 单独使用以及与 Pembrolizumab 联合治疗转移性黑色素瘤的 1 期临床试验
- 批准号:
10189528 - 财政年份:2017
- 资助金额:
$ 58.31万 - 项目类别:
A Phase 1 Clinical Trial Evaluating the Novel Small Molecule Immuno-Oncology Antagonist SX-682 Alone and With Pembrolizumab in Metastatic Melanoma
评估新型小分子免疫肿瘤拮抗剂 SX-682 单独使用以及与 Pembrolizumab 联合治疗转移性黑色素瘤的 1 期临床试验
- 批准号:
9755385 - 财政年份:2017
- 资助金额:
$ 58.31万 - 项目类别:
Phase II clinical evaluation of Omnitram in neuropathic pain
Omnitram 治疗神经病理性疼痛的 II 期临床评价
- 批准号:
8981655 - 财政年份:2015
- 资助金额:
$ 58.31万 - 项目类别:
Phase II clinical evaluation of Omnitram in neuropathic pain
Omnitram 治疗神经病理性疼痛的 II 期临床评价
- 批准号:
9317459 - 财政年份:2015
- 资助金额:
$ 58.31万 - 项目类别:
Efficacy and resistance mechanisms of LD-aminopterin in psoriasis
LD-氨基蝶呤治疗银屑病的疗效及耐药机制
- 批准号:
8792437 - 财政年份:2014
- 资助金额:
$ 58.31万 - 项目类别:
Efficacy and resistance mechanisms of LD-aminopterin in psoriasis
LD-氨基蝶呤治疗银屑病的疗效及耐药机制
- 批准号:
9188625 - 财政年份:2014
- 资助金额:
$ 58.31万 - 项目类别:
相似海外基金
How novices write code: discovering best practices and how they can be adopted
新手如何编写代码:发现最佳实践以及如何采用它们
- 批准号:
2315783 - 财政年份:2023
- 资助金额:
$ 58.31万 - 项目类别:
Standard Grant
One or Several Mothers: The Adopted Child as Critical and Clinical Subject
一位或多位母亲:收养的孩子作为关键和临床对象
- 批准号:
2719534 - 财政年份:2022
- 资助金额:
$ 58.31万 - 项目类别:
Studentship
A comparative study of disabled children and their adopted maternal figures in French and English Romantic Literature
英法浪漫主义文学中残疾儿童及其收养母亲形象的比较研究
- 批准号:
2633211 - 财政年份:2020
- 资助金额:
$ 58.31万 - 项目类别:
Studentship
A material investigation of the ceramic shards excavated from the Omuro Ninsei kiln site: Production techniques adopted by Nonomura Ninsei.
对大室仁清窑遗址出土的陶瓷碎片进行材质调查:野野村仁清采用的生产技术。
- 批准号:
20K01113 - 财政年份:2020
- 资助金额:
$ 58.31万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
A comparative study of disabled children and their adopted maternal figures in French and English Romantic Literature
英法浪漫主义文学中残疾儿童及其收养母亲形象的比较研究
- 批准号:
2436895 - 财政年份:2020
- 资助金额:
$ 58.31万 - 项目类别:
Studentship
A comparative study of disabled children and their adopted maternal figures in French and English Romantic Literature
英法浪漫主义文学中残疾儿童及其收养母亲形象的比较研究
- 批准号:
2633207 - 财政年份:2020
- 资助金额:
$ 58.31万 - 项目类别:
Studentship
The limits of development: State structural policy, comparing systems adopted in two European mountain regions (1945-1989)
发展的限制:国家结构政策,比较欧洲两个山区采用的制度(1945-1989)
- 批准号:
426559561 - 财政年份:2019
- 资助金额:
$ 58.31万 - 项目类别:
Research Grants
Securing a Sense of Safety for Adopted Children in Middle Childhood
确保被收养儿童的中期安全感
- 批准号:
2236701 - 财政年份:2019
- 资助金额:
$ 58.31万 - 项目类别:
Studentship
A Study on Mutual Funds Adopted for Individual Defined Contribution Pension Plans
个人设定缴存养老金计划采用共同基金的研究
- 批准号:
19K01745 - 财政年份:2019
- 资助金额:
$ 58.31万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Structural and functional analyses of a bacterial protein translocation domain that has adopted diverse pathogenic effector functions within host cells
对宿主细胞内采用多种致病效应功能的细菌蛋白易位结构域进行结构和功能分析
- 批准号:
415543446 - 财政年份:2019
- 资助金额:
$ 58.31万 - 项目类别:
Research Fellowships