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.

根据任务19，承包商应按照COR的指示进行体内或体外的特殊毒理学、安全性或药代动力学研究，其细节不能在授予合同之前具体说明。这些研究可能需要开发和表征一种模型，以便对潜在的药物治疗剂进行评估。这项研究的目的是确定测试物品与相互作用物品，例如滥用物质，如吗啡，对全身体积描记测量的呼吸参数的安全性。仅出于成本估算的目的，假设以下内容。测试品或其载体将通过口服途径给药，相互作用物品，例如吗啡或其载体，将通过植入的颈静脉插管通过静脉途径给药给药，给45只雄性和45只雌性SD大鼠，体重200-250克。应测量下列参数：呼吸频率(F)；潮气量(TVP)；分钟容量(MVB)；吸气时间(Ti)；呼气时间(Te)；吸气末暂停(EIP)；呼气末暂停(EEP)；室内温度(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(Nsigh)；呼吸暂停百分比(Papnea)；以及平均呼吸暂停持续时间(Tapnea)。将这些参数放入体积描记仪后，在受试物/车辆剂量前连续记录1h，并在1、2、5、10、15、30和60min报告；在测试物品/车辆剂量后2小时，并在给药后0、1、2、5、10、15、30、60、90和120分钟报告，以及在相互作用物品/车辆剂量后4小时报告，并在给药后0、1、2、5、10、15、30、60、90、120、150、180、210和240分钟用表格和使用1分钟箱的时间历程图报告。在体积描记仪中，每30分钟记录一次临床体征。应进行模拟给药环节，以使动物适应搬运和体积描记室。最后一篇互动文章录制后，动物们将被人道地献祭。应对试制品和相互作用制品给药溶液进行稳定性分析，并验证其身份和浓度。可能会有最多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。

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.