Defining “Best Practices” for Critical Endpoints in Preclinical Screening of New Chemical Entities for Ototoxicity Liability.
Ototoxicity has been defined as the tendency of certain
therapeutic agents and
other chemical substances to cause functional impairments and cellular degeneration of the
tissues of the inner ear resulting in hearing loss.
A literature review was conducted to assimilate study strategies that represent
“Industry Best Practices” for the conduct of preclinical ototoxicity evaluation for submission
to regulatory drug approval agencies.
We have proposed a systems-approach and protocol
criteria for the valid and
reliable assessment of auditory function that can be
easily included as a screening tool for
ototoxicity within the Tiered Structure of preclinical
assays required for approval of any
chemical entity targeted for human use.
There are over 130 drugs or drug combinations that
have a known risk liability for auditory
dysfunction in humans.
In 2001, Palomar Garcia et al conducted a comprehensive literature
review through 10 years of peer-reviewed publications
to investigate the prevalence of drug induced ototoxicity.
Cochlear and vestibular hair cell damage can be induced by numerous
other factors such as acoustic trauma, aging, blast wave, irradiation, infection, heavy metals,
pesticides, herbicides, organic solvents or gene mutations.
There are currently no systematic or regulatory requirements for any standard
preclinical studies conducted of new molecular entities that include analysis of all
peripheral and central vestibular structures or auditory sensory organs before drug approval.
Otolaryngol Open J. 2016; 2(2): 58-69. doi: 10.17140/OTLOJ-2-114
