DOSE-RESPONSE RELATIONSHIPS FOR FUROSEMIDE OTOTOXICITY IN RAT

Furosemide is an ototoxic loop diuretic which is highly bound to serum albumin. Previous studies have shown that rats deficient in albumin a re more susceptible to furosemide ototoxicity than are rats with norma l serum albumin concentrations: The present study was designed to comp are the dose-response relationships for furosemide ototoxicity in rats with normal serum albumin concentration to rats without albumin in th eir serum. Young adult rats 50-80 days of age from each group were ane sthetized with Rompun, and the endocochlear potential (EP) and compoun d action potential (CAP) thresholds were measured before and after fur osemide injection. After a stable EP and CAP threshold were measured, each animal was injected with a single dose of furosemide through a ca nnula in the jugular vein. Rats with normal serum albumin had very lit tle change in the EP or CAP threshold until the dose of furosemide was 40 mg/kg or greater. The dose-response curves for EP reduction and CA P threshold elevation then rose steeply to reach a maximum at 50 mg/kg . Albumin-deficient rats were much more sensitive to the effects of fu rosemide. The dose-response curves for both EP and CAP were shifted to the left. The doses resulting in half-maximal effects in the albumin- deficient rats were about half that found in the normal rats. These fi ndings support the hypothesis that the access of furosemide to its sit e of ototoxic action in the cochlea depends on the quantity of unbound furosemide in the serum.