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[Effect of fosfomycin on auditory organs and its transfer to cochlear lymph following application of its solution
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Fosfomycin (FOM) ototopical solution showed concentration-dependent transfer into cochlear lymph in guinea pigs, with a longer half-life than kanamycin (KM). No significant hair cell damage was observed with FOM treatment.
Area of Science:
- Ototopical drug delivery and pharmacokinetics
- Otolaryngology and audiology research
- Antibiotic efficacy and safety studies
Context:
- Middle ear infections require effective drug delivery to the inner ear.
- Understanding antibiotic penetration into cochlear lymph is crucial for treating inner ear infections.
- Ototopical solutions are a potential route for delivering therapeutics to the inner ear.
Purpose:
- To evaluate the transfer of fosfomycin (FOM) from the middle ear cavity to the cochlear lymph in guinea pigs.
- To compare the pharmacokinetic profile of FOM with kanamycin (KM) in the cochlear lymph.
- To assess the ototoxicity of FOM ototopical solutions on cochlear hair cells.
Summary:
- Male guinea pigs received ototopical fosfomycin (FOM) or kanamycin (KM) solutions. Cochlear lymph was analyzed for antibiotic concentrations, revealing FOM's concentration-dependent transfer and a longer half-life (4.8 hours) compared to KM (2.3 hours).
- Peak FOM concentration in cochlear lymph was lower than KM, but the area under the curve (AUC) for 3% FOM was higher, indicating sustained exposure.
- Scanning electron microscopy revealed no significant correlation between FOM treatment and damage to outer or inner hair cells, suggesting a favorable safety profile.
Impact:
- This study provides critical pharmacokinetic data for FOM ototopical solutions, informing potential therapeutic strategies for inner ear infections.
- The findings suggest FOM may offer a viable treatment option for otitis media with potential inner ear involvement.
- Demonstrates the importance of assessing drug transfer and ototoxicity for developing safe and effective ototopical therapies.