PURPOSE: To award Task Order No. 75N95019F00089 (Interaction Safety Studies in Rats with Whole Body Plethysmography). Period of Performance: 08/01/2019 to 07/31/2020.

目的：授予第 75N95019F00089 号任务令（通过全身体积描记法对大鼠进行相互作用安全性研究）。

• 批准号: 10286894
• 负责人: Laura Evans
• 金额: $ 1.2万
• 依托单位: SRI INTERNATIONAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10286894
• 关键词: Animals; Apnea; Award; Biological Assay; Body Weight; Cannulas; Clinical; Contractor; Contracts; Development; Dose; Drug Kinetics; Evaluation; Female; Graph; Guidelines; Hour; Humidity; Implant; In Vitro; Intravenous; Measures; Modeling; Morphine; National Institute of Drug Abuse; Oral; Performance; Plethysmography; Rattus; Reporting; Route; Safety; Specific qualifier value; Sprague-Dawley Rats; Structure of jugular vein; Temperature; Testing; Tidal Volume; Time; Toxicology; Whole Body Plethysmography; cost estimate; in vivo; male; respiratory; safety study

Under Task 19, the Contractor shall conduct, as directed by the COR, special in vivo or in vitro toxicology, safety or pharmacokinetic studies, the details of which cannot be specified in advance of the contract award. These studies may necessitate the development and characterization of a model that is amenable to the evaluation of potential pharmacotherapeutic agents. The objective of this study is to determine the safety of a test article in combination with an interaction article, for example, an abused substance, such as morphine, on respiratory parameters measured by whole body plethysmography. For purposes of cost estimation only, assume the following. A test article or its vehicle will be administered by the oral route and an interaction article, e.g., morphine or its vehicle, will be administered by the intravenous route, via an implanted jugular vein cannula, to 45 male and to 45 female Sprague Dawley rats, 200-250 g body weight. The following parameters shall be measured: respiratory rate (f); tidal volume (TVp); minute volume (MVb); inspiratory time (Ti); expiratory time (Te); end inspiratory pause (EIP); end expiratory pause (EEP); chamber temperature (Tc) and relative humidity (RH). The following apnea parameters may also be measured: sigh count (Nsigh); number of apneas (Napnea); apnea percentage (Papnea); and average apnea duration (Tapnea). After being placed in the plethysmograph, these parameters would be recorded continuously for 1 hour prior to the test article/vehicle dose and reported at 1, 2, 5, 10, 15, 30 and 60 min; for 2 hours after the test article/vehicle dose and reported at 0, 1, 2, 5, 10, 15, 30, 60, 90 and 120 min post dosing and for 4 hours after the interaction article/vehicle dose and reported at 0, 1, 2, 5, 10, 15, 30, 60, 90, 120, 150, 180, 210 and 240 min post dosing in tables and as time course graphs using 1 min bins. Clinical signs shall be recorded every 30 min whilst in the plethysmograph. There shall be a mock dosing session to acclimate the animals to handling and the plethysmography chambers. The animals will be humanely sacrificed after the last post interaction article recording. Test article and interaction article dosing solutions shall be assayed for stability and to verify identity and concentration. There may be up to 2 studies. NIDA requires a complete report for each study. Report content and format shall conform to GLP guidelines.

根据任务19，承包商应按照COR的指示进行特殊的体内或体外毒理学、安全性或药代动力学研究，其细节在授予合同之前无法规定。这些研究可能需要开发和表征一个模型，该模型适合于评价潜在的药物。本研究的目的是确定供试品与相互作用品（例如滥用物质，如吗啡）联合使用对全身体积描记法测量的呼吸参数的安全性。仅出于成本估算的目的，假设以下情况。供试品或其溶媒将通过经口途径给药，而相互作用品，例如，吗啡或其赋形剂将通过静脉途径，通过植入的颈静脉插管，给予45只雄性和45只雌性Sprague道利大鼠，200-250 g体重。应测量以下参数：呼吸频率（f）;潮气量（TVp）;分钟通气量（MVb）;吸气时间（Ti）;呼气时间（Te）;吸气末暂停（EIP）;呼气末暂停（EEP）;室温（Tc）和相对湿度（RH）。还可以测量以下呼吸暂停参数：叹息计数（Nsigh）;呼吸暂停次数（Napnea）;呼吸暂停百分比（Papnea）;和平均呼吸暂停持续时间（T呼吸暂停）。置于体积描记器中后，在供试品/溶剂给药前1小时连续记录这些参数，并在1、2、5、10、15、30和60 min时报告;供试品/溶媒给药后2小时，并在0、1、2、5、10、15、30、60、给药后90和120 min以及相互作用供试品/溶媒给药后4小时，并在0、1、2、5、10、15、30、60、90、120、150、180、表格中的给药后210和240 min以及使用1 min分组的时间过程图。在体积描记器中，应每30分钟记录一次临床体征。应进行模拟给药阶段，以使动物适应处理和体积描记室。在记录最后一次相互作用后供试品后，人道处死动物。应测定供试品和相互作用品给药溶液的稳定性，并验证鉴别和浓度。最多可以有2项研究。NIDA要求每项研究都有一份完整的报告。报告内容和格式应符合GLP指南。