Elimination kinetics of furosemide in perilymph and serum of the chinchilla. Neuropharmacologic correlates

Abstract

This study was done to determine the comparative elimination kinetics of furosemide from chinchilla perilymph and serum, and to correlate perilymph concentration with changes in endocochlear potential. The elimination kinetics of furosemide (FU) were determined in sera and perilymph obtained from chinchillas injected with 100 mg/kg i.v. of FU. Concentrations of FU exhibited a linear decay pattern in serum and perilymph over the initial 60 minutes. The rate of decline of furosemide levels in perilymph was about four times slower than the rate of fall in serum. Chronic treatment (25 mg/kg i.p. every 12 hours) did not appear to influence the level of drug at 60 minutes after a dose of FU (100 mg/kg IV). Chinchillas were also studied following doses of FU ranging from 25--200 mg/kg i.v. to see the effect on endocochlear potential (EP). A positive correlation was found between FU dosage, the maximum millivolt reduction of EP and the time to initiation of recovery of EP. The perilymph concentration of furosemide when the EP began to recover was 5 microgram/ml (1.5 x 10(-5) M). Knowledge of furosemide kinetics may ultimately be applied to prevent ototoxicity in patients.