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To evaluate the use of respiratory ″head out″ plethysmographys for use as a respiratory function assessment tool in rats as part of the respiratory system assessment required under the ICH S7A guideline.Morphine(20 mg·kg-1 iv) and Theophylline(10 mg·kg-1 iv) were selected for use as reference compounds in this study.Male SpragueDawley rats,approximately 7-8 weeks of age and in the weight range 246-303 g were selected as the test system.An approximate one week acclimation period preceded the study,during which animals were pre-selected for the suitability by assessment of their ability to stay in the restraint chambers(″head-out″ plethysmographys) for a target of about 2.5 h-Any rat demonstrating excessive excitability or abnormal breathing patterns were removed from the study.On the day of dosing,animals were placed in ″head out″ plethysmographs and allowed to acclimate to the chambers for at least 5 min prior to each data collection period.Immediately following the acclimation period,ventilatory parameters(tidal volume,respiratory rate,and derived respiratory minute volume(RMV) were measured for an approximate 15 min period predose,continuously for the following approximate 2.5 h,then for approximate 15 min at approximately 4 and 24 h postdose.Results obtained were consistent with the literature and based on the results of this study,this assay,using respiratory ″head out″ plethysmographys to assess respiratory function,is considered acceptable for use in Pulmonary assessments under the ICH guideline.
To evaluate the use of respiratory “head out” plethysmographys for use as a respiratory function assessment tool in rats as part of the respiratory system assessment required under the ICH S7A guideline. Morphine (20 mg · kg-1 iv) and Theophylline (10 mg · Kg-1 iv) were selected for use as reference compounds in this study. Male Sprague Dawley rats, approximately 7-8 weeks of age and in the weight range 246-303 g were selected as the test system. An approximate one week acclimation period preceded the study, during which animals were pre-selected for the suitability by assessment of their ability to stay in the restraint chambers (“head-out” plethysmographys) for a target of about 2.5 h-Any rat demonstrating excessive excitability or abnormal breathing patterns were removed from the study. On the day of dosing, animals were placed in “head out” plethysmographs and allowed to acclimate to the chambers for at least 5 min prior to each data collection period. Immediately following the accli mation period, ventilatory parameters (tidal volume, respiratory rate, and derived respiratory minute volume (RMV) were measured for an approximate 15 min period predose, continuously for the following approximate 2.5 h, then for approximate 15 min at approximately 4 and 24 h postdose . Results obtained were consistent with the literature and based on the results of this study, this assay, using respiratory “head out” plethysmographys to assess respiratory function, is considered acceptable for use in Pulmonary assessments under the ICH guideline.