Effect of diet-ingested pirfenidone on pulmonary function, cardiovasculature and blood gas measurements in rats.
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.
Mansoor
J K
JK
Department of Physical Therapy, School of Pharmacy, University of the Pacific, Stockton, CA 95211, USA. jmansoor@uop.edu
Chen
A T
AT
Schelegle
E S
ES
Giri
S
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D005105:Expiratory Reserve Volume / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006909:Hydroxyproline / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011728:Pyridones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012115:Residual Volume / Q000187:drug effects; D012119:Respiration / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011728:Pyridones; C093844:pirfenidone; D006909:Hydroxyproline