通过减少动物使用来完善法规呼吸数据
regulatory respiratory data refinement with reduced animal usage
通过减少动物使用来完善法规呼吸数据
author links open overlay panellouisesladen a,1, rommel mathesonb, kevin nortonb, aileen milnec,1
a safety and adme translational sciences department, drug safety and metabolism, imed biotech unit, astrazeneca, unit 310, cambridge science park, milton road, cambridge cb4 0fz, uk
bcharles river, safety pharmacology,transcanadienne, senneville, qc h9x 3r3, canada
ccharles river, safety pharmacology, elphinstone research centre, tranent, edinburgh eh33 2ne, united kingdom
abstract introduction
assessment of effects of potential drug candidates on the respiratory system is part of the regulatory preclinical safety assessment conducted prior to first in human trials (ftih). commonly, this is carried out utilizing head out plethysmography (hop) or whole body plethysmography (wbp) which record only ventilatory parameters. when dosing via the inhaled route a more thorough respiratory assessment, including a direct measure of airway mechanics, is desirable. the aim of the present work was to improve the strategy for respiratory safety testing by a) evaluating a emetered pleural pressure – hop (pp-hop) model and b) evaluating a crossover study design protocol in the wbp model to reduce variability and animal usage.
评估潜在候选药物对呼吸系统的影响是在*人体试验(ftih)之前进行的临床前安全性评估的一部分。一般情况下，这是利用头颅容积描记术(hop)或全身容积描记术(wbp)进行的，后者只记录通气参数。通过吸入途径给药时，需要进行更*的呼吸评估，包括直接测量气道力学。本研究的目的是通过a)评估遥测胸膜压-跳(pp-hop)模型和b)评估wbp模型中的交叉研究设计方案来改善呼吸安全性测试策略，以减少变异性和动物使用。
methods
for the pp- hop model, rats were surgically implanted with a emetry device for measurement of pleural pressure. animals were placed in hop tubes and respiratory function assessed when exposed to methacholine at doses of 0 (saline only), 0.42, 1.6 and 3.8?mg/kg. wbp assessment was performed in rats in a crossover study design when treated with theophylline at doses of 0 (saline only), 3, 10 and 30?mg/kg.
在pp-hop模型中，大鼠被外科植入遥测装置以测量胸膜压。将动物置于啤酒花管中，在0(仅生理盐水)、0.42、1.6和3.8?mg/kg剂量下暴露于乙酰*时评估呼吸功能。在交叉研究设计中，当*剂量为0(仅生理盐水)、3、10和30?mg/kg时，对大鼠进行wbp评估。
results
data from the pp-hop study confirmed the expected changes in ventilatory parameters and airway mechanics in response to inhaled methacholine, including an increase in pulmonary resistance and decrease in tidal volume.
data from the wbp crossover study demonstrated similar sensitivity and statistical power to detect changes in respiratory rate and tidal volume to a standard parallel group design.
pp-hop研究的数据证实了吸入甲基*后通气参数和气道力学的预期变化，包括肺阻力增加和潮气量减少。
来自wbp交叉研究的数据显示，检测呼吸频率和潮气量变化的敏感性和统计能力与标准平行组设计相似。
conclusion
measurement of pp-hop in a stand-alone safety pharmacology study in conjunction with hop assessment conducted as part of a toxicology study, represents an improved respiratory testing strategy for inhaled drugs. for compounds administered by other routes, we conclude that use of wbp using a crossover dosing design is a suitable alternative to parallel dosing groups, with a significant reduction in animal numbers and no loss of statistical power.
在一个独立的安全药理学研究中，pp-hop的测量与作为毒理学研究的一部分的hop评估相结合，代表了一种改进的吸入药物呼吸测试策略。对于通过其他途径给药的化合物，我们得出结论，使用交叉给药设计的wbp是平行给药组的合适替代方案，动物数量显著减少，且不丧失统计能力。
abbreviations
ftih first time in human
pp-hop pleural pressure-head out plethysmography
wbp whole body plethysmography
i.t. intra tracheal
vt tidal volume
bpm breaths per minute
mv minute volume
ich the international council for harmonisation of technical requirements for pharmaceuticals for human use
glp good laboratory practice
SR2-30F阻旋式料位开关水平安装
生活污水处理设备200吨/天
深圳光明区到太原货运专线直达,深圳光明区到太原物流专线
走在时尚的木材粉碎机设备xcl新成木材粉碎机厂家
5G带来3C自动化和半导体产业新机遇
通过减少动物使用来完善法规呼吸数据
南京到横州货运专线物流包车_南京到横州物流公司
武汉武昌区到新河货运专线_专业武汉武昌区到邢台新河专线物流公司
成都到贵阳货运公司_成都到贵阳物流专线_贵阳货运专线
淮安到常州物流专线_淮安到常州物流公司专线货运
义乌到文昌货运公司,义乌到文昌物流专线返程车配货
玉米棒成“童年记忆” 膨化机保证营养健康是趋势
江门到安宁物流专线_江门到安宁物流公司专线直达
强调FFESTO费斯托气动调节阀的安装细节与技巧
增强网抗腐蚀性能检测仪使用方法
平湖到广平物流货运公司_平湖到邯郸广平专线物流公司直达运输
上海嘉定区到无极货运专线_专业上海嘉定区到石家庄无极专线物流公司
福州到中牟货运专线_优质福州到郑州中牟物流专线公司
溧阳到博尔塔拉物流公司专线运输,溧阳到博尔塔拉物流专线
广州越秀区到南昌青山湖区专线物流公司_广州越秀区到青山湖区专线货运
通过减少动物使用来完善法规呼吸数据
author links open overlay panellouisesladen a,1, rommel mathesonb, kevin nortonb, aileen milnec,1
a safety and adme translational sciences department, drug safety and metabolism, imed biotech unit, astrazeneca, unit 310, cambridge science park, milton road, cambridge cb4 0fz, uk
bcharles river, safety pharmacology,transcanadienne, senneville, qc h9x 3r3, canada
ccharles river, safety pharmacology, elphinstone research centre, tranent, edinburgh eh33 2ne, united kingdom
abstract introduction
assessment of effects of potential drug candidates on the respiratory system is part of the regulatory preclinical safety assessment conducted prior to first in human trials (ftih). commonly, this is carried out utilizing head out plethysmography (hop) or whole body plethysmography (wbp) which record only ventilatory parameters. when dosing via the inhaled route a more thorough respiratory assessment, including a direct measure of airway mechanics, is desirable. the aim of the present work was to improve the strategy for respiratory safety testing by a) evaluating a emetered pleural pressure – hop (pp-hop) model and b) evaluating a crossover study design protocol in the wbp model to reduce variability and animal usage.
评估潜在候选药物对呼吸系统的影响是在*人体试验(ftih)之前进行的临床前安全性评估的一部分。一般情况下，这是利用头颅容积描记术(hop)或全身容积描记术(wbp)进行的，后者只记录通气参数。通过吸入途径给药时，需要进行更*的呼吸评估，包括直接测量气道力学。本研究的目的是通过a)评估遥测胸膜压-跳(pp-hop)模型和b)评估wbp模型中的交叉研究设计方案来改善呼吸安全性测试策略，以减少变异性和动物使用。
methods
for the pp- hop model, rats were surgically implanted with a emetry device for measurement of pleural pressure. animals were placed in hop tubes and respiratory function assessed when exposed to methacholine at doses of 0 (saline only), 0.42, 1.6 and 3.8?mg/kg. wbp assessment was performed in rats in a crossover study design when treated with theophylline at doses of 0 (saline only), 3, 10 and 30?mg/kg.
在pp-hop模型中，大鼠被外科植入遥测装置以测量胸膜压。将动物置于啤酒花管中，在0(仅生理盐水)、0.42、1.6和3.8?mg/kg剂量下暴露于乙酰*时评估呼吸功能。在交叉研究设计中，当*剂量为0(仅生理盐水)、3、10和30?mg/kg时，对大鼠进行wbp评估。
results
data from the pp-hop study confirmed the expected changes in ventilatory parameters and airway mechanics in response to inhaled methacholine, including an increase in pulmonary resistance and decrease in tidal volume.
data from the wbp crossover study demonstrated similar sensitivity and statistical power to detect changes in respiratory rate and tidal volume to a standard parallel group design.
pp-hop研究的数据证实了吸入甲基*后通气参数和气道力学的预期变化，包括肺阻力增加和潮气量减少。
来自wbp交叉研究的数据显示，检测呼吸频率和潮气量变化的敏感性和统计能力与标准平行组设计相似。
conclusion
measurement of pp-hop in a stand-alone safety pharmacology study in conjunction with hop assessment conducted as part of a toxicology study, represents an improved respiratory testing strategy for inhaled drugs. for compounds administered by other routes, we conclude that use of wbp using a crossover dosing design is a suitable alternative to parallel dosing groups, with a significant reduction in animal numbers and no loss of statistical power.
在一个独立的安全药理学研究中，pp-hop的测量与作为毒理学研究的一部分的hop评估相结合，代表了一种改进的吸入药物呼吸测试策略。对于通过其他途径给药的化合物，我们得出结论，使用交叉给药设计的wbp是平行给药组的合适替代方案，动物数量显著减少，且不丧失统计能力。
abbreviations
ftih first time in human
pp-hop pleural pressure-head out plethysmography
wbp whole body plethysmography
i.t. intra tracheal
vt tidal volume
bpm breaths per minute
mv minute volume
ich the international council for harmonisation of technical requirements for pharmaceuticals for human use
glp good laboratory practice
SR2-30F阻旋式料位开关水平安装
生活污水处理设备200吨/天
深圳光明区到太原货运专线直达,深圳光明区到太原物流专线
走在时尚的木材粉碎机设备xcl新成木材粉碎机厂家
5G带来3C自动化和半导体产业新机遇
通过减少动物使用来完善法规呼吸数据
南京到横州货运专线物流包车_南京到横州物流公司
武汉武昌区到新河货运专线_专业武汉武昌区到邢台新河专线物流公司
成都到贵阳货运公司_成都到贵阳物流专线_贵阳货运专线
淮安到常州物流专线_淮安到常州物流公司专线货运
义乌到文昌货运公司,义乌到文昌物流专线返程车配货
玉米棒成“童年记忆” 膨化机保证营养健康是趋势
江门到安宁物流专线_江门到安宁物流公司专线直达
强调FFESTO费斯托气动调节阀的安装细节与技巧
增强网抗腐蚀性能检测仪使用方法
平湖到广平物流货运公司_平湖到邯郸广平专线物流公司直达运输
上海嘉定区到无极货运专线_专业上海嘉定区到石家庄无极专线物流公司
福州到中牟货运专线_优质福州到郑州中牟物流专线公司
溧阳到博尔塔拉物流公司专线运输,溧阳到博尔塔拉物流专线
广州越秀区到南昌青山湖区专线物流公司_广州越秀区到青山湖区专线货运