Mansoor J K, Chen A T, Schelegle E S, Giri S
Department of Physical Therapy, School of Pharmacy, University of the Pacific, Stockton, CA 95211, USA.
Res Commun Mol Pathol Pharmacol. 1999 Mar;103(3):260-8.
Pirfenidone is an antifibrotic drug that we have shown attenuates the increase in collagen buildup in hamsters exposed to bleomycin, in turn reducing pulmonary function and blood gas decrements seen in this model of interstitial pulmonary fibrosis. The systemic effects of pirfenidone ingestion, however, are unknown. We examined the effect of diet-ingested pirfenidone on pulmonary function, systemic and pulmonary cardiovasculature and blood gas measurements, breathing pattern and lung hydroxyproline content in rats fed either a control diet or a diet containing 0.5% pirfenidone. Residual volume was higher and expiratory reserve volume lower in the pirfenidone group, with no change in functional residual capacity. Tidal volume was also lower in the pirfenidone group, with no change in the overall level of ventilation. There was a trend toward a reduced hydroxyproline content and an increased lung compliance in the pirfenidone group. There were no differences in systemic or pulmonary pressures, cardiac output, stroke volume, heart rate, pH or blood gases between the two groups. These data indicate that pirfenidone has few systemic side-effects but may have a mild effect on the basal level of lung collagen content with resulting clinical changes in some pulmonary function measurements and changes in breathing pattern.
吡非尼酮是一种抗纤维化药物，我们已证明它能减轻博来霉素处理的仓鼠体内胶原蛋白堆积的增加，进而减少这种间质性肺纤维化模型中出现的肺功能和血气下降。然而，口服吡非尼酮的全身效应尚不清楚。我们研究了在对照饮食或含0.5%吡非尼酮饮食喂养的大鼠中，饮食摄入吡非尼酮对肺功能、全身及肺血管系统、血气测量、呼吸模式和肺羟脯氨酸含量的影响。吡非尼酮组的残气量较高，呼气储备量较低，功能残气量无变化。吡非尼酮组的潮气量也较低，通气总量无变化。吡非尼酮组有肺羟脯氨酸含量降低和肺顺应性增加的趋势。两组之间的全身或肺压力、心输出量、每搏输出量、心率、pH值或血气无差异。这些数据表明，吡非尼酮几乎没有全身副作用，但可能对肺胶原蛋白含量的基础水平有轻微影响，从而导致一些肺功能测量值的临床变化和呼吸模式的改变。
