Eprazinone therapy improves pulmonary function and arterial pO2 in patients with
chronic bronchitis; however, the mechanism of action is unknown. The purpose of this study was to determine if
eprazinone alters either lung
surfactant levels in bronchoalveolar lavage fluid (BAL) of normal rats, or ion transport across canine tracheal epithelium mounted in Ussing chambers. In the
surfactant studies, normal rats were force fed three doses (50, 100, and 200 mg/kg) of
eprazinone for 4 days.
Eprazinone at a dose of 200 mg/kg significantly increased total and individual (with the exception of
phosphatidylinositol)
phospholipid levels and decreased total neutral
lipids. Lower doses of
eprazinone significantly decreased neutral
lipid levels without affecting the
phospholipids. There was no change in BAL levels of
protein or cells and no abnormal histology. In airway epithelial studies, mucosal addition of
eprazinone produced a dose-dependent partially reversible decrease in short-circuit current (Isc). The decrease in Isc at lower
eprazinone concentrations was accounted for entirely by a decrease in net
chloride secretion while at higher concentrations both
sodium and
chloride transport were affected. Submucosal
eprazinone had no affect on ion transport. These studies suggest that
eprazinone influences both BAL
lipid levels and ion transport, either of which could lead to a beneficial
therapeutic effect.