Noise-induced hearing loss (NIHL) is a global health problem affecting over 5% of the population worldwide. We have shown\npreviously that acute noise-induced cochlear injury can be ameliorated by administration of drugs acting on adenosine receptors\nin the inner ear, and a selective A1 adenosine receptor agonist adenosine amine congener (ADAC) has emerged as a potentially\neffective treatment for cochlear injury and resulting hearing loss. This study investigated pharmacokinetic properties ofADACin rat\nperilymph after systemic (intravenous) administration using a newly developed liquid chromatography-tandem mass spectrometry\ndetection method. The method was developed and validated in accordance with the USA FDA guidelines including accuracy,\nprecision, specificity, and linearity. Perilymph was sampled from the apical turn of the cochlea to prevent contamination with\nthe cerebrospinal fluid. ADAC was detected in cochlear perilymph within two minutes following intravenous administration and\nremained in perilymph above its minimal effective concentration for at least two hours. The pharmacokinetic pattern of ADAC\nwas significantly altered by exposure to noise, suggesting transient changes in permeability of the blood-labyrinth barrier and/or\ncochlear blood flow. This study supports ADAC development as a potential clinical otological treatment for acute sensorineural\nhearing loss caused by exposure to traumatic noise.
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