Abstract
Male guinea pigs were given 0.1 ml of 2, 3 or 5% fosfomycin (FOM) ototopical solution once a day for 5 days into a middle ear cavity through artificially perforated ear drum Kanamycin A (KM) was used at 2% ototopical solution as control drug Four animals of each group were sacrificed under pentobarbital anesthesia to isolate the cochlea 10 days after the final application The cochlea was washed with 0.1 M phosphate buffer (pH 7.0), followed by fixing with 2.5% glutaraldehyde and 1% osmic acid Cochlear specimens were prepared by standard method for scanning electron microscopic observation The scanning electron microscopic observations revealed some damages in outer and inner hair cells, such as partial deformation or loss of auditory hair in hair cells, but these damages were not correlated to drug treatments.
In order to determine the transfer of FOM and KM from middle ear cavity to cochlear lymph in male guinea pigs, the cochlear lymph was collected 0.5, 1, 2 and 4 hours after an application of 0.1 ml of 3 or 5% FOM and 2% KM ototopical solution into a middle ear cavity, followed by estimating content of these antibiotics in the lymph The results showed the peak concentration in lymph at 1 to 2 hours after an application of 3% FOM was lower than that after 2% KM, but the AUC of 3% FOM was higher than that of 2% KM The AUC value of FOM was dependent on the applied concentration of FOM The value of half-life time was about 4.8 hours at FOM and about 2.3 hours at KM.
These results suggest that FOM is freely diffused from applied middle ear cavity into cochlear lymph and distributed for longer time than KM, but FOM exerts no toxic effect on the cochlear hair cells in guinea pigs.
