Postauricular gentamicin administration does not provide preferential inner-ear delivery in guinea pigs

Whether postauricular injection provides preferential access to the inner ear relative to conventional systemic administration remains uncertain. We used gentamicin as an ototoxic model drug to compare postauricular, intramuscular and intratympanic injection through a surgically created posterior tympanotomy in guinea pigs.

Forty-eight male guinea pigs were studied in repeated-dose and single-dose experiments. In the repeated-dose experiment, gentamicin was administered postauricularly or intramuscularly every 12 h for 7 days (14 injections). Auditory brainstem response (ABR) thresholds, cochlear outer hair cells (OHC), body weight, serum creatinine, and blood urea nitrogen were assessed. In the single-dose experiment, animals received gentamicin by intratympanic injection through a posterior tympanotomy, postauricular injection, or intramuscular injection. OHC morphology and perilymph gentamicin concentrations were evaluated at 2.5 and 12.5 h.

Repeated postauricular and intramuscular administration produced comparable bilateral ABR threshold elevations and extensive OHC loss, together with body-weight reduction and renal dysfunction; no significant between-route differences were detected for these outcomes. At 12.5 h after a single administration, moderate OHC loss was observed only after intratympanic injection. Perilymph gentamicin concentrations at 2.5 h were 4,103 ± 349 μg/mL after intratympanic injection, 18.43 ± 4.70 μg/mL after postauricular administration, and 21.84 ± 16.75 μg/mL after intramuscular administration. At 12.5 h, the respective concentrations were 416.20 ± 109.10, 10.86 ± 5.98, and 11.58 ± 7.88 μg/mL. Postauricular and intramuscular concentrations did not differ significantly at either time point.

Postauricular gentamicin injection did not provide preferential access to the inner ear compared with intramuscular injection. Under the conditions of this guinea pig model, its cochlear and systemic effects were consistent with systemic exposure rather than targeted local delivery that bypassed the blood-labyrinth barrier (BLB).