목적: We have recently described positive findings following treatment of cochlear otosclerosis with systemic bisphosphonates in human. Also, we have successfully delivered a fluorescently labeled compound of zoledronate (6-FAMZOL) using a local delivery via the round window membrane or through a cochleostomy. We tried different molar concentrations of zoledronate to find out the ototoxicity of zoledronate and report our ototoxicity data of intracochlear zoledronate delivery over a short-term and a long-term period. 방법:Male albino guinea pigs weighing 350g were treated with Artificial perilymph (AP) or zoledronate plus 6-FAMZOL by direct intracochlear injection. A Harvard Apparatus PHD 2000 Infusion Syringe Pump was used to introduce zoledronate plus 6-FAMZOL into the guinea pig cochlea. A 500 μL glass syringe was connected via polyetherether ketone tubing to an 11mm length of PTFE tubing. A small bleb was fabricated at a point 3mm from the distal end. AP and two different molar concentrations of zoledronate plus a small amount of 6-FAMZOL (4% and 8% of human systemic dose) were tested. DPOAE and CAP were monitored before injection, immediately after injection, 4 hours later, and 4 weeks later. We analyzed the animals by embedding the temporal bones within resin and grinding them down to a mid-modiolar section, followed by fluorescent microscopy. 결과:Drug delivery up to the apical turn was confirmed in all animals comparing the fluorescent images between animals treated with AP and those treated with zoledronate plus 6-FAMZOL. Hearing was preserved in animals treated with AP or 4% of human systemic dose. At 8% of human systemic dose, CAP threshold between 8kHz and 24kHz was elevated following 40 minutes' intracochlear delivery by 20dB while DPOAE threshold remained stable compared with that of animals treated with AP. 결론:Intracochlear delivery of bisphosphonates can be achieved without incurring ototoxicity. The optimal effective dose in guinea pigs is 4% of human systemic dose.