Comparison of systemic and otic administration of ofloxacin.
OBJECTIVE
To assess the feasibility of delivering ofloxacin across the intact tympanic membrane; to compare middle ear bioavailability of ofloxacin after otic and systemic administrations; to determine distribution of otically delivered ofloxacin to other tissues.


METHODS
A prospective, controlled animal study.


METHODS
Rats underwent surgery wherein the middle ear cavity was opened and filled with saline. An equivalent amount of ofloxacin was delivered intraperitoneally or into the external ear canal. Saline within the middle ear was sampled and completely replaced in 15-minute intervals for 3 hours. Blood was collected twice after the initial application of ofloxacin for high-performance liquid chromatography (HPLC). Animals were sacrificed 3 hours after the initial addition of ofloxacin; the temporal bones were harvested for histological analysis; urine and colon mucosa were collected for HPLC analysis.


RESULTS
Both systemic and otic applications led to a comparable accumulation of ofloxacin in the middle ear over the 3-hour period after the initial administration. The pharmacokinetics of ofloxacin penetration into the middle ear was sporadic and subject-dependent. Both methods of administration led to drug accumulation in blood serum, urine, and colonic mucosa.


CONCLUSIONS
Topical application of ofloxacin to the intact tympanic membrane allows for drug penetration into the middle ear space. Similar middle ear ofloxacin levels could be achieved with systemic and topic applications, but drug concentrations were inconsistent. The accumulation of ofloxacin in other tissues suggests applications designed to be ototopical may also result in systemic absorption.
Koulich
Elena
E
Department of Otolaryngology HNS, University of Texas Southwestern Medical Center, Dallas UT Southwestern, Dallas, Texas 75390-9035, USA. Elena.Koulich@utsouthwestern.edu
Roland
Peter S
PS
Pawlowski
Karen S
KS
D000287:Administration, Topical; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005240:Feasibility Studies; D008297:Male; D015242:Ofloxacin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011446:Prospective Studies; D051381:Rats; D017207:Rats, Sprague-Dawley; D014432:Tympanic Membrane
D015242:Ofloxacin