The impact of different dosing regimens of the aminoglycosides netilmicin and amikacin on vestibulotoxicity in the guinea pig

Abstract

The purpose of this study was to assess whether vestibulotoxicity caused by aminoglycoside antibiotics is influenced by the treatment schedule used: i.e., a single high dose given once daily (o.d.) vs multiple divided doses (tres in die, t.i.d.). Two groups of guinea pigs (5 animals/group) were injected intramuscularly for 21 days with either netilmicin or amikacin 150 mg/kg o.d., whereas other groups received each drug at 50 mg/kg t.i.d. at 8-h intervals. Amikacin was also given at 225 mg/kg o.d. and 75 mg/kg t.i.d. Vestibular functions were assessed by measuring vestibulo-ocular reflexes. Acoustic function was also evaluated by measuring Preyer's pinna reflex. Sensory epithelia of the inner ears were evaluated histologically under a scanning electron microscope. Netilmicin failed to affect either the vestibular or the acoustic apparatus in the animal groups receiving the two dosing regimens. Amikacin in a dose of 150 mg/kg per day induced an acoustic deficit which was more severe in the t.i.d. group. The higher dose of amikacin provoked significant lesions of acoustic and vestibular function, irrespective of the dosing regimen used. These data suggest that the o.d. dosing regimen of the aminoglycoside antibiotics might provide effective treatment for infectious diseases without enhancing the risk for vestibular and acoustic side effects.

Pharmacokinetics and renal toxicity of three once-a-day doses of amikacin in cows

“…This scheme often requires pharmacokinetic expertise and close monitoring of drug serum levels and renal function to guide dosage adjustments to maximise efficacy and minimise toxicity (Pettarossi et al, 1990;Magdesian et al, 1998;Tudor et al, 1999). Other important disadvantages associated with the standard dosing of aminoglycosides include sub-therapeutic dosing, stress, inaccurate timing of drug administration and blood sampling, and misinterpretation of drug levels (Brown and Riviere, 1991).…”

“…Pulse dosing or high-peak-extendedinterval dosing of aminoglycosides was first used by Labowitz et al (1974) in man and it has been accepted that there is no significant difference in safety between pulse dosing and multiple-dose regimes (Galloe et al, 1995;Barza et al, 1996;Ferriols-Lisart and Alós-Almiñana, 1996). Furthermore, efficacy is thought to be superior when using pulse dosing of aminoglycosides (Tran Ba Huy and Deffrennes, 1988;Pettarossi et al, 1990;Campbell et al, 1996).…”

Effect of gentamicin dosing interval on therapy of viridans streptococcal experimental endocarditis with gentamicin plus penicillin

“…Various approaches to reducing aminoglycosideassociated nephrotoxicity while maintaining clinical efficacy have been investigated and include reducing the total daily dose, use of possibly less-toxic agents, and increasing the dosing interval for aminoglycoside administration. Increasing the dosing interval has been shown to be no more toxic than is intermittent administration (3,7,11,18,21,30,(33)(34)(35)(36)(37)(41)(42)(43). The efficacy of this approach has been tested with experimental gram-negative rod infections (9, 19, 21, 24-26, 31, 43), penicillin-susceptible (6,16,38) or -resistant (6, 16) viridans streptococcal and enterococcal (15) experimental endocarditis, and human infections other than endocarditis (4,14,20,23,27,36,39,40).…”

Aminoglycoside Dosing Regimen and Pharmacokinetic Parameters in the Guinea Pig

“…We therefore studied the auditory and vestibular effects of OD regimen ver sus the conventional 3 daily injections (TID regimen) of two representative am inoglycosides, netilmicin and amikacin, in the guinea pig [10,11]. To support func tional studies we designed an experiment to evaluate the effect of the dosing sched ule on pharmacokinetic parameters and to assess possible accumulation phenomena after multiple dosing.…”