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.