Effect of Bumetanide Upon Endolymphatic Potential of Guinea Pigs

Abstract

The effect of bumetanide upon the endolymphatic potential (EP) was examined using 46 healthy guinea pigs and following results were obtained. i) Within a few minutes after intravenous administration of this drug, the EP started to decline rapidly. After reaching the lowest level, the EP started to recover. This recovery could be devided into two phases, namely the initial rapid recovery and the later very slow one.The recovery up to the original level was not obtained in any case for 3 hours observation and the EP recovered to the level of only 30 to 40 mV in cases of a large dose administration (30 to 40 mg/kg).2) The minimal dose required to affect the EP was 5 mg/kg and the reduction of the EP became larger as the given dose increased. The maximum reduction (the reduction to about -40 mV) was obtained at the dose of 30 mg/kg or more .3) When the EP reached the lowest level, 20 animals put into ichemic condition by aorta section. The decline rate of the EP in the bumetanide intoxicated animals was much slower than that of the normal ones and approximately proportional to the lowest level reduced by bumetanide. When the lowest level was less than -20 mV, ischemia elevated the EP instead of reducing.These results were discussed combining our previous studies on furosemide and ethacrynic acid. In conclusion, the effect of bumetanide upon the cochlea is almost identical to ethacrynic acid and slightly different from furosemide, and taking the diuretic action into consideration, the present study indicates that bumetanide is less ototoxic than the other two.

Interaction of Bumetanide and Kanamycin

“…Therefore, when clinical dosages of the two drugs are considered, the relative ototoxic potency of BUN is 0.11-0.16 that of FM. ' Kusakari et al (1977) described that, in guinea pigs, the endocochlear potential was significantly affected by BUN at dose levels of 5 mg/kg, compared to dose levels of 20-30 mg/kg for FM. It would follow that BUN is approximately 0.1 times as potent as FM in causing cochlear dysfunction, when allowed for their relative diuretic potency.…”

“…Bumetanide (BUN) is a new potent loop diuretic, and its absolute diuretic potency is 4 0 -6 0 times that of FM (0ster-gaard et al, 1972;Oleson et al, 1973;Davies et al, 1974). But when clinical dosages of the two drugs are compared, the relative ototoxic potency of BUN is only about 1/10 of FM {Brown, 1975;Kusakari et al, 1977).…”