Pharmacokinetics of caroverine and its protective and therapeutic roles in noise-induced hearing loss following round window administration in the guinea pig

Abstract

Caroverine, an N-methyl-D-aspartate and I?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist together with antioxidant activity, is effective in the treatment of certain inner ear disorders. Local caroverine application onto the round window membrane could be more effective and avoid systemic side effects. We investigated the pharmacokinetics of caroverine in the perilymph, cerebrospinal fluid and plasma after systemic and local administrations in guinea pigs by using high-performance liquid chromatography. Auditory brainstem responses were measured to evaluate auditory functional effect. The results showed that local application was a both safe and efficient method. The following studies used the established local method to test the protective and therapeutic effects of caroverine against noise trauma. We found caroverine could significantly protect and rescue hearing when applied prior to or 1 h after noise exposure. Thus, pharmacological protection of the cochlea against noise is possible and may be of great clinical potential.