An implantable semiannual antipsychotic delivery system

描述（由申请人提供）：背景：药物依从性是精神分裂症复发和再住院的最高决定因素。因此，使患者能够长期服药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概念验证长期植入式输送系统。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更可取。研究项目：根据之前的评论，目前的建议是在进行更昂贵的毒理学、行为和分子表征研究之前，用2年的时间来证明灭菌的可生物降解利培酮植入物的体外/体内相关模型。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Aim将展示一种原型抗精神病药物的体外释放特性，这种药物是由8种聚合物在单一药物负荷下制成的无菌植入物。第二个目的是测定每一种单聚合物植入物的体内利培酮血清浓度。路易斯·杜布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。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。该项目与宾夕法尼亚大学材料科学系的Karen I. Winey博士有长期合作关系。研究人员现在具备临床精神病学、精神药理学和聚合物工程方面所需的专业知识和背景，以完成拟议的研究计划。工业研发和药代动力学建模顾问已加入，以进一步扩大研究团队。未来的研究将评估长期皮下给药系统的毒理学效应，以及评估分子、神经化学和行为方面的措施，以彻底评估利培酮植入物的长期效应。拟议研究的完成将促进未来对多种药物长期递送系统的工业投资，从而显著改善未来的患者护理。

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.