THE RENAL HANDLING OF ZOXAZOLAMINE (FLEXIN)

¹ Department of Pharmacology, State University of New York, Upstate Medical Center, Syracuse, New York

The renal excretion of zoxazolamine, a powerful uricosuric agent in man, is known to be low. The present study is an attempt to determine whether this low excretion is attributable to active reabsorption, which could explain the uricosuric effect on the basis of competition, or to passive diffusion out of the tubule. The following evidence obtained in dogs suggests that zoxazolamine diffuses through tubular epithelium with extraordinary facility and that this accounts for low clearance. First, renal clearance of zoxazolamine is linearly related to urinary flow rate. Second, clearance is independent of plasma level over a range extending to 82 µg/ml. Third, the ratios of zoxazolamine concentrations in urine and in corresponding ultrafiltrates of plasma were nearly unity under all conditions studied. The pKa of zoxazolamine was determined (3.25) and is too low for urinary pH to have any influence on excretion rate. The drug is not uricosuric in dogs.