Ofloxacin otic solution in patients with otitis media: an analysis of drug concentrations

To measure the concentration of ofloxacin in otorrhea, serum, and middle ear mucosa after topical administration of 0.3% ofloxacin otic solution.

Study of 0.3% ofloxacin otic solution administered in a single dose of 0.5 mL in adults or 0.25 mL in children with chronic suppurative otitis media and perforated tympanic membrane, with serial sampling of otorrhea and serum up to 8 hours after dosing and middle ear mucosa up to 2 hours after dosing.

Three hospitals in Kagoshima, Japan.

Thirty-eight patients (age range, 3-81 years) with chronic suppurative otitis media and perforated tympanic membrane; 20 patients had sampling of otorrhea and serum and 18 patients (who required middle ear surgery) had middle ear mucosa and serum sampling.

High concentrations of ofloxacin were measured in otorrhea samples taken immediately after dosing, followed by a rapid, nonlogarithmic decline. Elimination of the drug through otorrhea was believed to be related to loss from the application site with ear drainage, rather than to biologic mechanisms. Maximum concentration of ofloxacin in otorrhea was seen at the initial sampling time, 30 minutes after dosing, with concentrations measured up to the last sampling at 8 hours. Very low concentrations of ofloxacin were found in serum after topical administration of the drug. Concentrations were not detected in serum samples of most of the patients. The highest concentration measured was 10 ng/mL. Drug concentrations were detected primarily in samples obtained up to 1 hour after the dose was administered. Mucosal drug concentrations were highly variable, ranging from nondetectable to 602 pg/g. For the 6 bacterial strains isolated from the middle ear, the highest minimum inhibitory concentration of ofloxacin was covered by otorrhea drug concentrations measured at up to 8 hours after dosing in some patients. No adverse events were observed. No clinically significant adverse changes in laboratory test results or audiometric results were observed.

Drug concentrations were high in otorrhea, very low or not detected in serum, and highly variable in middle ear mucosa. Nonbiologic loss of the drug with the ear drainage through the external auditory canal and eustachian tube was probably related to the high concentration in otorrhea samples. Drug concentrations in middle ear mucosa suggest that the drug reaches the infection site.