Comparative uptake of gentamicin, netilmicin, and amikacin in the guinea pig cochlea and vestibule

Author:

Dulon D,Aran J M,Zajic G,Schacht J

Abstract

The kinetics of the entry of three aminoglycosides into inner-ear tissues of the guinea pig after acute and chronic administration were compared: gentamicin toxic to the cochlea and the vestibule, amikacin preferentially cochleotoxic, and netilmicin of low ototoxic liability. During constant intravenous infusion, levels of the three drugs in plasma tended to reach a plateau after 1 h, while levels in perilymph did not reach a plateau within 6 h. The drug concentrations in both vestibular and cochlear tissues quickly reached saturation. Amikacin and gentamicin concentrations were similar in vestibular and cochlear tissues, while netilmicin values were somewhat lower. After 1 week of chronic treatment (100 mg of drug per kg of body weight daily subcutaneously), levels of gentamicin and amikacin in tissue were similar to each other and were not significantly different between cochlear and vestibular tissues. Netilmicin concentrations again were somewhat lower in the tissues, but identical to those of the other drugs in the perilymph. After 3 weeks of treatment, all of the drugs were equally distributed in the inner-ear tissues. Release of the drug from the tissues after the 3-week treatment was faster for amikacin (83% decrease after 20 days) than for netilmicin and gentamicin (approximately 50% decrease). There was no correlation, under any of the experimental conditions, between the drug concentrations and their degrees of toxicity. These results demonstrate that selective aminoglycoside ototoxicity cannot be explained by a preferential uptake or accumulation of drugs in the afflicted tissues or in the perilymph.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Reference25 articles.

1. Aran J. M. 1982. Aminoglycosides cochlear and vestibular action p. 377-386. In J. P. Fillastre (ed.) Nephrotoxicityototoxicity of drugs. Editions I.N.S.E.R.M. Paris.

2. Auditory function in guinea pigs treated with netilmicin and other aminoglycosides;Arpini A.;Arch. Otolaryngol.,1979

3. Distribution of radioactive dihydrostreptomycin in the cochlea;Balog K.;Ann. Otol. Rhinol. Laryngol.,1970

4. Relationship between rat renal accumulation of gentamicin, tobramycin, and netilmicin and their nephrotoxicities;Brier M. E.;Antimicrob. Agents Chemother.,1985

5. Brummett R. E. and K. E. Fox. 1982. Studies of aminoglycoside ototoxicity in animal models p. 419-451. In A. Whelton and H. C. Neu (ed.) The aminoglycosides: microbiology clinical use and toxicology. Marcel Dekker Inc. New York.

Cited by 71 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3