Effect of isepamicin dosing scheme on concentration in cochlear tissue

Area of Science:

• Ototoxicity and Pharmacology
• Inner Ear Drug Delivery

Background:

• Aminoglycosides are crucial antibiotics but can cause ototoxicity.
• Understanding drug concentration in cochlear tissue is vital for safe and effective dosing.

Purpose of the Study:

• To evaluate if different dosing regimens of isepamicin affect its concentration in guinea pig cochlear tissues.
• To assess the impact of continuous infusion versus once-daily injection on inner ear drug levels.

Main Methods:

• Two groups of guinea pigs received daily subcutaneous isepamicin for eight days.
• One group received continuous infusion, the other a single daily injection.
• Isepamicin concentrations were measured in cochlear duct and nerve tissues; auditory brain stem responses (ABR) and creatinine levels were monitored.

Main Results:

• No significant differences in isepamicin concentration were found between continuous infusion and once-daily injection groups in either cochlear duct or nerve.
• No signs of renal insufficiency or hearing impairment (ABR changes) were observed in either group.
• Median concentrations in cochlear duct were 2.40 µg/mg protein (continuous) vs. 2.50 µg/mg protein (once-daily).
• Median concentrations in cochlear nerve were 1.93 µg/mg protein (continuous) vs. 2.59 µg/mg protein (once-daily).

Conclusions:

• Isepamicin exhibits linear uptake kinetics in inner ear tissues, irrespective of the dosing scheme.
• The findings suggest that both continuous infusion and once-daily injection may be viable for achieving therapeutic concentrations without significant ototoxicity.
• Results may guide optimized clinical dosing strategies for aminoglycosides to minimize cochlear damage.