An implantable semiannual antipsychotic delivery system

植入式半年一次抗精神病药物输送系统

• 批准号: 7194618
• 负责人: STEVEN J SIEGEL
• 金额: $ 19.77万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-15 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7194618
• 关键词: Academia; Address; Affinity; Antipsychotic Agents; Behavioral; Binding; Biological Assay; Characteristics; Chemistry; Clinical; Collaborations; Consultations; Data; Development; Doctor of Philosophy; Drug Kinetics; Engineering; Environment; Exercise; Family Physicians; Feedback; Fostering; Funding; Future; Glycolic-Lactic Acid Polyester; Goals; Haloperidol; Hematology; Human; Implant; Implantable Infusion Pumps; In Vitro; Individual; Industry; Intervention; Investments; Laboratories; Link; Long-Term Effects; Methods; Modeling; Modification; Molecular; National Institute of Mental Health; Outcome; Patient Care; Patients; Pattern; Pennsylvania; Pharmaceutical Preparations; Polymers; Process; Prolactin; Property; Psychiatry; Psychopharmacology; Relapse; Research; Research Personnel; Research Project Grants; Risperidone; Schizophrenia; Science; Serum; Specific qualifier value; Standards of Weights and Measures; Sterility; System; Testing; Therapeutic; Toxic effect; Toxicology; Uncertainty; United States Food and Drug Administration; Universities; Viscosity; Western Blotting; atypical antipsychotic; base; behavior measurement; concept; cost; design; drug synthesis; improved; in vivo; medication compliance; neurochemistry; neurotechnology; novel; novel strategies; pharmacokinetic model; polylactic acid-polyglycolic acid copolymer; programs; protein expression; prototype; receptor; receptor binding; research and development; response; simulation; subcutaneous; therapy development

DESCRIPTION (provided by applicant): Background: Medication nonadherence is the highest determinant of relapse and rehospitalization in schizophrenia. Therefore, interventions that empower patients to remain on medication for extended periods would substantially improve clinical outcomes using existing medications. The investigators previously developed a proof of concept long-term implantable delivery system using the typical antipsychotic agent haloperidol. Need: However, feedback from patients, families and physicians indicates that a long-term delivery system using a newer atypical antipsychotic medication would be preferable. Research Project: In response to previous reviews, the current proposal is now limited to 2 years to demonstrate an in vitro/in vivo correlation model for sterilized biodegradable Risperidone implants before proceeding to more costly toxicological, behavioral and molecular characterization studies. Studies were designed in consultation with the FDA Psychopharmacology team and would be performed in collaboration with the NIMH drug synthesis program. The first Aim will demonstrate in vitro release characteristics for a prototype antipsychotic medication from sterile implants made from 8 polymers at a single drug load. The second Aim will determine in vivo Risperidone serum concentration from each of these single-polymer implants. Dr. Louise Dube has joined our team to bring expertise in Clinical Psychopharmacology for ADME modeling. Environment: Studies will be conducted at the Center for Experimental Therapeutics in Psychiatry at the University of Pennsylvania under the direction of Steven J. Siegel MD, PhD. This program has a longstanding collaboration with Dr. Karen I. Winey in the Department of Material Science at The University of Pennsylvania. Investigators now have the required expertise and background in clinical psychiatry, Psychopharmacology and polymer engineering to accomplish the proposed research program. Industry R&D and pharmacokinetic modeling consultants have been included to further augment the research team. Future studies would evaluate the toxicological effects of a long-term subcutaneous delivery system as well as assessing molecular, neurochemical and behavioral measures to thoroughly evaluate long-term effects of Risperidone implants. Completion of the proposed studies would foster future industrial investment in long-term delivery systems for multiple agents, leading to dramatically improved patient care in the future.

描述（由申请人提供）：背景：药物不依从性是精神分裂症复发和再住院的最高决定因素。因此，使患者能够长期保持药物治疗的干预措施将大大改善使用现有药物的临床结果。研究人员先前开发了一种使用典型抗精神病药物氟哌啶醇的长期植入式给药系统的概念验证。需求：然而，来自患者、家属和医生的反馈表明，使用较新的非典型抗精神病药物的长期给药系统将是优选的。研究项目：作为对之前审查的回应，目前的提案限制为2年，以证明灭菌的可生物降解利培酮植入物的体外/体内相关性模型，然后再进行更昂贵的毒理学、行为和分子表征研究。研究是在与FDA精神药理学小组协商后设计的，并将与NIMH药物合成计划合作进行。第一个目标将证明原型抗精神病药物的体外释放特性，无菌植入物由8种聚合物制成，单一载药量。第二个目标将确定这些单聚合物植入物中每种的体内利培酮血清浓度。Louise Dube博士加入了我们的团队，为ADME建模带来了临床精神药理学方面的专业知识。工作环境：研究将在宾夕法尼亚大学精神病学实验治疗中心进行，由Steven J. Siegel医学博士指导。该项目与凯伦博士有着长期的合作关系。宾夕法尼亚大学材料科学系的Winey说。研究人员现在拥有所需的专业知识和背景，在临床精神病学，精神药理学和聚合物工程，以完成拟议的研究计划。包括行业研发和药代动力学建模顾问，以进一步扩大研究团队。未来的研究将评价长期皮下给药系统的毒理学效应，并评估分子、神经化学和行为指标，以彻底评价利培酮植入剂的长期效应。完成拟议的研究将促进未来对多种药物长期输送系统的工业投资，从而大大改善未来的患者护理。