Abstract
Hearing loss affects >5% of the global population and therefore, has a great social and clinical impact. Sensorineural hearing loss, which can be caused by different factors, such as acoustic trauma, aging, and administration of certain classes of drugs, stems primarily from a dysfunction of the cochlea in the inner ear. Few therapeutic strategies against sensorineural hearing loss are available. To develop effective treatments for this disease, it is crucial to precisely determine the behavior of ototoxic and therapeutic agents in the microenvironment of the cochlea in live animals. Since the 1980s, a number of studies have addressed this issue by different methodologies. However, there is much less information on pharmacokinetics in the cochlea than that in other organs; the delay in ontological pharmacology is likely due to technical difficulties with accessing the cochlea, a tiny organ that is encased with a bony wall and has a fine and complicated internal structure. In this review, we not only summarize the observations and insights obtained in classic and recent studies on pharmacokinetics in the cochlea but also describe relevant analytical techniques, with their strengths, limitations, and prospects.
Highlights
Audition is an essential sensation for animals
Vibrations of the cochlear partition stimulate hair cells, which are classified into inner- and outer hair cells
High-performance liquid chromatography (HPLC), LC-MS, and an immunoassay with sampled perilymph and endolymph are the methods frequently used for quantifying drug concentrations in these cochlear fluids over time
Summary
Audition is an essential sensation for animals. Humans can hear sounds at diverse frequencies ranging from 20 to 20,000 Hz and perceive a millionfold difference in sound pressure level (Hudspeth, 2014). Vibrations of the cochlear partition stimulate hair cells, which are classified into inner- and outer hair cells Both types of cells have their cell bodies immersed in perilymph, whereas their apical surfaces are exposed to endolymph. Excitation of outer hair cells changes the length of the cell bodies This somatic motility can mechanically amplify oscillations of the cochlear partition (Ashmore, 2008; Fettiplace, 2020). K+-enriched endolymph (Békésy, 1952; Dallos, 1996; Hibino et al, 2010; Hudspeth, 2014; Nin et al, 2016) This endocochlear potential (EP) accelerates sound-induced K+ entry from endolymph into hair cells: the process that triggers neurotransmission in inner hair cells and somatic motility in outer hair cells. The hearing impairment is reversed by discontinuation of drug administration in many cases but sometimes becomes
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