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: 7330354
• 负责人: STEVEN J SIEGEL
• 金额: $ 21.03万
• 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/7330354
• 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：药物不遵守是精神分裂症中复发和复发的最高决定因素。因此，使用现有药物的干预措施将使患者保持长时间的药物治疗将大大改善临床结果。研究人员先前使用典型的抗精神病药氟哌啶醇开发了概念证明的长期植入式递送系统。需求：但是，患者，家庭和医生的反馈表明，使用新型非典型抗精神病药物的长期分娩系统是可取的。研究项目：针对先前的评论，目前的提案现在仅限于2年，以证明在进行更为昂贵的毒理学，行为和分子表征研究之前，用于灭菌生物降解的可生物降解的利培酮植入物的体内/体内相关模型。研究是与FDA心理药理学团队协商的研究，并将与NIMH药物合成计划合作进行。第一个目的将证明从单个药物负荷下由8种聚合物制成的无菌植入物的原型抗精神病药物的体外释放特性。第二个目标将确定这些单聚合物植入物的体内利培酮血清浓度。路易斯·杜贝（Louise Dube）博士加入了我们的团队，为ADME建模带来了临床心理药理学的专业知识。环境：研究将在宾夕法尼亚大学的精神病学实验治疗中心在史蒂文·J·西格尔医学博士的指导下进行。该计划与宾夕法尼亚大学材料科学系的Karen I. Winey博士进行了长期合作。现在，研究人员拥有临床精神病学，心理药理学和聚合物工程的必要专业知识和背景，以完成拟议的研究计划。已经包括行业研发和药代动力学建模顾问，以进一步增加研究团队。未来的研究将评估长期皮下递送系统的毒理作用，并评估分子，神经化学和行为措施，以彻底评估利培酮植入物的长期影响。拟议研究的完成将促进多个代理商的长期交付系统的未来工业投资，从而导致将来的患者护理大大改善。