Perilymphatic concentration of gentamicin administered intratympanically in guinea pigs

Intratympanic gentamicin therapy has recently become popular for Meniere's disease, although the administration protocol remains controversial. To date, few studies have been conducted regarding the pharmacokinetics of drugs administered intratympanically. We measured gentamicin concentration in the perilymph close to the round window membrane using a microdialysis technique. A bolus of 0.5 mg gentamicin was put on the round window membrane or a clinically used solution of 5 mg gentamicin was placed in the tympanic bulla of guinea pigs. After 56 +/- 21 min of bolus administration, gentamicin concentration reached a maximum level of 2900 +/- 1200 microg/ml and then decreased, with a half-life of 117 +/- 47 min, characteristic of the kinetics expected with a one-compartment model. With solution administration, the maximum concentration did not differ, but the time to the maximum concentration and the half-life in the perilymph were longer, compared with the results of bolus administration. Our results suggest that even solution administration of gentamicin, which is simple and repeatable, provides a sufficient, stable and continuous supply to the perilymph.