THE EXPERIMENTAL STUDY ON THE OTOTOXICITY OF AMIKACIN
WITH THERAPEUTIC DOSES IN NEONATAL GUINEA-PIGS
Xu HM, Wang SY
Children’s Hospital
of Chongqing University of Medical sciences，Chongqing, China
Objective: To
clarify the possibility of ototoxicity of aminoglycosides in different age
groups of guinea pigs (expecially in premature and neonatal animals) given
amikacin (AMK) with therapeutic doses.
Methods: AMK
was intramuscularly injected with a dose of 65mg/kg (equal to the
therapeutic doses clinically) once a day in 14 days for neonatal, infant
and adult groups with 48 guinea pigs in each, 15 in premature group. Of
them, 5~8 guinea pigs in each group were sacrificed for
histological examination of cochlea with microscopy and scanning
electron-microscopy (SEM) on the 3rd, 5th, 7th,
10th and 14th day with the drug administration,as well the 28th、60th day. There were 6
guinea pigs in each age groups for control.
Results: On
histological study for cochlea, many stereocilia were lain down or
disappeared as early as the 3rd day and outer hair cells were absent on the
5th day in either premature or neonatal group under observation with SEM.
The numbers of absent hair cells in neonatal group were more than those in
infant and adult groups after the 7th day under microscopic observation
(P<0.05 or P<0.01). The absent hair cells in infant group was more
than those in adults after 28th day (P<0.05). Continuous loss of hair
cells was well seen on the 28th day after the drug had been stopped in two
weeks.
Conclusion: Significant
ototoxicity of AMK to cochlea was well showed in baby guinea pigs with
various severity, particularly in premature and neonatal animals even with
therapeutic doses equal to clinical use. The severity of cochlear damage
was getting worse with a prolonged course of the administration. The damage
of cochlea could be continuously increased in a quite longer period after
the drug stopped.