کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2592439 | 1132020 | 2010 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Respiratory safety pharmacology: Concurrent validation of volume, rate, time, flow and ratio variables in conscious male Sprague–Dawley rats Respiratory safety pharmacology: Concurrent validation of volume, rate, time, flow and ratio variables in conscious male Sprague–Dawley rats](/preview/png/2592439.png)
This study compares basic respiratory variables (rate, tidal and minute volumes) with time-, flow- and ratio-derived parameters obtained using head-out plethysmography in rats following administration of reference drugs (isotonic saline, 2.0 mL/kg, IV; albuterol, 400 μg/kg, inhalation; methacholine, 136 μg/kg, IV; and remifentanil, 14 μg/kg, IV) to identify respiratory variables with superior sensitivity. Paired t-tests by block-period, and analysis of covariance (ANCOVA) with baseline as covariate and a posteriori pair-wise comparisons using Dunnett’s test were used. Variations in respiratory parameters observed over time justify the use of a control group in any respiratory safety pharmacology study for inter-groups comparison. Handling-, and slumbering-, induced perturbations were minimal. The system was sensitive and specific to detect changes in respiratory variables related to pharmacologically-induced bronchodilation, bronchoconstriction and central respiratory depression. The standard variables (respiratory rate, tidal and minute volumes) confirmed to be the cornerstone of respiratory safety pharmacology to detect pharmacological changes. Flow-derived parameters appeared as highly valuable complement for interpretation of respiratory response, whereas time- and ratio-derived parameters presented limited added value during interpretation.
Journal: Regulatory Toxicology and Pharmacology - Volume 58, Issue 3, December 2010, Pages 444–450