Isosorbide Concentration in Perilymph of the Guinea Pig After Oral Administration Versus That After Round Window Perfusion

ABSTRACT

OBJECTIVES: The aims of this study were to investigate the feasibility of isosorbide delivery into perilymph through the round window membrane (RWM), and to compare the intracochlear isosorbide concentration in perilymph after oral administration (PO) versus that after round window perfusion (RWP). METHODS: Sixteen male guinea pigs (32 ears) were used. Isosorbide, an osmotic diuretic, was administered via RWP or PO. First, to investigate the optimal perfusion time, perilymph sampling of scala tympani from the RWM was performed after RWP for 15, 30, or 60 minutes. Second, to compare the drug concentration after RWP versus that after PO, perilymph was aspirated at 3 and 6 hours after administration. Intracochlear concentration of isosorbide was analyzed by high-performance liquid chromatography coupled to refractive index detection. RESULTS: Isosorbide passed through the RWM into perilymph after RWP. After RWP for 15, 30, and 60 minutes, mean isosorbide concentrations in perilymph were 116.27+/-44.65, 245.48+/-112.84, and 279.78+/-186.32 mM, respectively. The intracochlear concentration after RWP for 30 minutes was higher than that after RWP for 15 minutes (P=0.043). At 3 and 6 hours after PO, isosorbide concentrations in perilymph were 28.88+/-4.69 and 12.67+/-2.28 mM, respectively. In contrast, the corresponding concentrations after RWP were 117.91+/-17.70 and 75.03+/-14.82 mM at 3 and 6 hours, respectively. Isosorbide concentrations in perilymph following RWP were significantly higher than those following PO at both 3 and 6 hours (P=0.025 and P=0.034, respectively). CONCLUSION: Isosorbide can rapidly pass through the RWM after RWP in guinea pigs, and 30 minutes of perfusion is considered to be appropriate. In addition, over a 6-hour period, RWP can deliver higher concentrations of isosorbide into perilymph than those achieved with PO.