Effect of Dosing Schedule on Aminoglycoside Ototoxicity: Comparative Cochlear Ototoxicity of Amikacin and Isepamicin

Abstract

The effect of the dosing schedule on aminoglycoside ototoxicity was investigated in the guinea pig. The animals were given amikacin or isepamicin either by once-daily intramuscular injection of 200 mg/kg or by twice-daily injections of 100 mg/kg for 28 days. The once-daily treatment induced a lesser degree of ototoxicity than the twice-daily injections, which may indicate that the once-daily treatment therapy has a potential value in the clinical use of aminoglycoside antibiotics. Isepamicin sulfate is a new aminoglycoside antibiotic currently undergoing clinical investigation. This study revealed that isepamicin also has ototoxic properties as has been observed in all other aminoglycosides. The degree of ototoxicity, however, was markedly less than that of amikacin.

Temporal variation in nephrotoxicity of low doses of isepamicin in rats

“…In terms of renal toxicity, isepamicin compared favorably with amikacin given at low doses in rats (30). Moreover, Takumida et al (34) showed in guinea pigs that the once-daily treatment with amikacin and isepamicin induced a lesser degree of ototoxicity than the twice-daily injection but that the degree of ototoxicity induced by isepamicin was markedly less than that of amikacin.…”

Attenuation of Aminoglycoside Ototoxicity by Glutathione

“…Attempts to elucidate the mechanism of toxicity or to prevent the adverse effects have previously been unsuccessful. Recent studies have revealed that the once-daily treatment regimen of aminoglycosides induces the lowest degree of ototoxicity and have confirmed the efficacy and safety of a once-daily regimen for clinical use [3,4], Prevention of ototoxicity using several kinds of drugs, however, has been unsuccessful [7,8],…”

“…The degree of damage de pends not only on the particular antibiotic used but also on the dose schedule and the total dose [3,4], Concerning this group of drugs, comparative studies of ototoxicity KARGER ©1996 S. Karger AG. Basel 0301-1569/96/0582-0068S 10.00/0 E-Mail kargcr@kargcr.ch F ax+ 41 61 306 12 34 patterns have revealed that the most pronounced changes are found after neomycin treatment, whereas the least changes are evident after netilmicin treatment [1,2], Recent studies have also revealed that the dosing schedule also influences the development of ototoxicity [3,4], A once-daily dose therapy has recently been suggested for clinical use instead of an administration of aminoglyco side 2 or 3 times per day. This may be partly explained by better patient compliance, which is also convenient for the physician [5], A number of studies have confirmed the efficacy and safety of a once-daily regimen for clinical use [5,6], The risk of ototoxic development has been signifi cantly lower in a once-daily treatment than one given 2 or 3 times per day [4].…”

In vitro Activity of Isepamicin (Sch 21420), a New Aminoglycoside

“…However, the low therapeutic/toxic ratio of ex isting aminoglycosides like streptomycin, gen tamicin, netilmicin, tobramycin and amikacin has led to a search for safer drugs. Isepamicin is a semi-synthetic drug derived from genta micin B which is expected to have a clinical ef ficacy similar to that of amikacin but with less toxicity [1][2][3]. In this paper we describe the in vitro activity of isepamicin and compare it to amikacin against relatively resistant clinical isolates from a tertiary-care center.…”