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Citations to this article

Kinetics of gentamicin uptake and release in the rat. Comparison of inner ear tissues and fluids with other organs.
P Tran Ba Huy, … , P Bernard, J Schacht
P Tran Ba Huy, … , P Bernard, J Schacht
Published May 1, 1986
Citation Information: J Clin Invest. 1986;77(5):1492-1500. https://doi.org/10.1172/JCI112463.
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Research Article

Kinetics of gentamicin uptake and release in the rat. Comparison of inner ear tissues and fluids with other organs.

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Abstract

The kinetics of entry and release of gentamicin was investigated in fluids and tissues of the inner ear of the rat, as well as in renal cortex, and in organs that do not share susceptibility to the toxic effects of aminoglycosides. Various modes of administration were used to achieve different patterns of drug plasma concentrations. Electrophysiological and histological examinations were performed to correlate pharmacokinetics and ototoxicity. Results show that: the uptake of the drug by the inner ear tissues is dose dependent and manifests a rapid saturation kinetics with a concentration plateau of about 1 micrograms/mg of protein. The low ratio of the perilymph and endolymph to plasma concentrations argues against the concept of an accumulation of the drug in the inner ear over drug levels in plasma, which has been considered as the basic mechanism of ototoxicity. In renal cortex, the kinetics appears similar to that of the inner ear but the concentrations achieved are 10-fold higher than in cochlear tissues. In other organs (liver, heart, lung, and spleen), no saturation could be demonstrated within the duration of the experiment. Ototoxicity seems to be related to the penetration of the drug into compartment(s) from which the half-life of disappearance is extremely slow. Rapid uptake, early saturation, and long exposure of the tissues to the drug may account for the development of toxicity in inner ear and kidney.

Authors

P Tran Ba Huy, P Bernard, J Schacht

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Total citations by year

Year: 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 1996 1995 1994 1993 1992 1991 1990 1989 1988 1987 1986 1981 Total
Citations: 2 1 6 3 4 8 6 7 6 7 1 10 2 11 7 10 5 3 2 5 4 3 5 7 3 6 3 9 7 7 6 6 3 6 5 6 6 2 1 1 202
Citation information
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Citations to this article in year 2013 (10)

Title and authors Publication Year
Bumetanide hyperpolarizes madin-darby canine kidney cells and enhances cellular gentamicin uptake by elevating cytosolic Ca(2+) thus facilitating intermediate conductance Ca(2+)--activated potassium channels
T Wang, YQ Yang, T Karasawa, Q Wang, A Phillips, BC Guan, KT Ma, M Jiang, DH Xie, PS Steyger, ZG Jiang
Cell Biochemistry and Biophysics 2013
Evaluation of the Protective Effect of Beta Glucan on Amikacin Ototoxicity Using Distortion Product Otoacoustic Emission Measurements in Rats
T Bayindir, A Filiz, M Iraz, S Kaya, M Tan, MT Kalcioglu
Clinical and Experimental Otorhinolaryngology 2013
Memantine’s action against aminoglycoside-induced ototoxicity
P Pavlidis, J Maurer, E Apostolidou, G Kekes, D Kouvelas
European Archives of Oto-Rhino-Laryngology 2013
Receptor-Mediated Endocytosis across Human Placenta: Emphasis on Megalin
AA Akour, MJ Kennedy, P Gerk
Molecular Pharmaceutics 2013
Haschek and Rousseaux's Handbook of Toxicologic Pathology
BR Berridge, JF van Vleet, E Herman
Haschek and Rousseaux's Handbook of Toxicologic Pathology 2013
Cochlear pharmacokinetics of cisplatin: An in vivo study in the guinea pig: Cochlear Pharmacokinetics of Cisplatin
V Hellberg, I Wallin, H Ehrsson, G Laurell
The Laryngoscope 2013
A novel role of cytosolic protein synthesis inhibition in aminoglycoside ototoxicity
SP Francis, J Katz, KD Fanning, KA Harris, BD Nicholas, M Lacy, J Pagana, PF Agris, JB Shin
The Journal of neuroscience : the official journal of the Society for Neuroscience 2013
Gentamicin Concentration Gradients in Scala Tympani Perilymph following Systemic Applications
H Hahn, AN Salt, U Schumacher, SK Plontke
Audiology and Neurotology 2013
The Effect of Intratympanic Methylprednisolone and Gentamicin Injection on Ménière’s Disease
N Gabra, I Saliba
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery 2013
Extracellular Ca 2+ and Mg 2+ modulate aminoglycoside blockade of mechanotransducer channel-mediated Ca 2+ entry in zebrafish hair cells: an in vivo study with the SIET
LY Lin, W Pang, WM Chuang, GY Hung, YH Lin, JL Horng
American journal of physiology. Cell physiology 2013

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