Pharmacokinetic Properties of Adenosine Amine Congener in Cochlear Perilymph after Systemic Administration

Author:

Chang Hao1ORCID,Telang Ravindra S.1ORCID,Sreebhavan Sreevalsan2,Tingle Malcolm3ORCID,Thorne Peter R.1,Vlajkovic Srdjan M.1ORCID

Affiliation:

1. Department of Physiology and Centre for Brain Research, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand

2. Auckland Cancer Research Centre, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand

3. Department of Pharmacology, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand

Abstract

Noise-induced hearing loss (NIHL) is a global health problem affecting over 5% of the population worldwide. We have shown previously that acute noise-induced cochlear injury can be ameliorated by administration of drugs acting on adenosine receptors in the inner ear, and a selective A1adenosine receptor agonist adenosine amine congener (ADAC) has emerged as a potentially effective treatment for cochlear injury and resulting hearing loss. This study investigated pharmacokinetic properties of ADAC in rat perilymph after systemic (intravenous) administration using a newly developed liquid chromatography-tandem mass spectrometry detection method. The method was developed and validated in accordance with the USA FDA guidelines including accuracy, precision, specificity, and linearity. Perilymph was sampled from the apical turn of the cochlea to prevent contamination with the cerebrospinal fluid. ADAC was detected in cochlear perilymph within two minutes following intravenous administration and remained in perilymph above its minimal effective concentration for at least two hours. The pharmacokinetic pattern of ADAC was significantly altered by exposure to noise, suggesting transient changes in permeability of the blood-labyrinth barrier and/or cochlear blood flow. This study supports ADAC development as a potential clinical otological treatment for acute sensorineural hearing loss caused by exposure to traumatic noise.

Funder

Deafness Research Foundation of New Zealand

Publisher

Hindawi Limited

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

Cited by 5 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

1. Auckland hearing science discovery and translation in purinergic signaling and inner ear therapeutics;Journal of the Royal Society of New Zealand;2024-06-03

2. Sensorineural hearing loss and cognitive impairment: three hypotheses;Frontiers in Aging Neuroscience;2024-02-28

3. Purinergic Signalling in the Cochlea;International Journal of Molecular Sciences;2022-11-28

4. Purinergic signaling in the organ of Corti: Potential therapeutic targets of sensorineural hearing losses;Brain Research Bulletin;2019-09

5. Purinergic Signaling and Cochlear Injury-Targeting the Immune System?;International Journal of Molecular Sciences;2019-06-18

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