Clin Exp Otorhinolaryngol.  2014 Dec;7(4):281-285. 10.3342/ceo.2014.7.4.281.

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

• Kim M
• Do KH
• Kim KS

• KMID: 2278368
• DOI: http://doi.org/10.3342/ceo.2014.7.4.281

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.

Keyword

Isosorbide; Osmotic diuretics; Meniere disease; Round window

MeSH Terms

Administration, Oral*
Animals
Chromatography, Liquid
Diuretics, Osmotic
Guinea Pigs*
Humans
Isosorbide*
Male
Membranes
Meniere Disease
Perfusion*
Perilymph*
Refractometry
Scala Tympani
Diuretics, Osmotic
Isosorbide

Figure

• 

  Fig. 1 Perilymph sampling and quantitative analysis. (A) Demonstration of perilymph sampling at the round window of guinea pig temporal bone on the left side. (B) Glucose (arrowhead) and isosorbide (arrow) peaks detected by high-performance liquid chromatography coupled to refractive index detection.

• 

  Fig. 2 Isosorbide concentration after round window perfusion according to perfusion time. Lines in boxes are means, ends of boxes are quartiles, and whiskers show the range of values. *P<0.05.

• 

  Fig. 3 Isosorbide concentrations after oral administration (light gray) versus those after round window perfusion (dark gray). Lines in boxes are means, ends of boxes are quartiles, and whiskers show the range of values. *P<0.05.

Reference

1. Kitahara M, Takeda T, Yazawa Y, Matsubara H, Kitano H. Treatment of Ménière's disease with isosorbide. ORL J Otorhinolaryngol Relat Spec. 1982; 44(4):232–238. PMID: 7110671.

2. Juhn SK, Prado S, Pearce J. Osmolality changes in perilymph after systemic administration of glycerin. Arch Otolaryngol. 1976; 11. 102(11):683–685. PMID: 985201.

3. Kakigi A, Takeda T, Saito H, Kataoka H. Effect of isosorbide on hearing loss due to endolymphatic hydrops. Acta Otolaryngol Suppl. 1995; 519:223–226. PMID: 7610874.

4. Takeda T, Takeuchi S, Saito H. Effect of glycerol on pressure differences between perilymph and endolymph. Acta Otolaryngol. 1990; Jul-Aug. 110(1-2):68–72. PMID: 2386035.

5. Kakigi A, Takeda S, Takeda T, Sawada S, Azuma H, Higashiyama K, et al. Time course of dehydrating effects of isosorbide on experimentally induced endolymphatic hydrops in guinea pigs. ORL J Otorhinolaryngol Relat Spec. 2004; 66(6):291–296. PMID: 15668526.

6. Klockhoff I. Diagnosis of Menière's disease. Arch Otorhinolaryngol. 1976; 9. 212(4):309–314. PMID: 990081.

7. Padoan S. Oral versus i.v. administration of the glycerol test: side-effects and usefulness. Acta Otolaryngol. 2003; 5. 123(4):482–487. PMID: 12797582.

8. Matsubara H, Kitahara M, Takeda T, Yazawa Y. Rebound phenomenon in glycerol test. Acta Otolaryngol Suppl. 1984; 419:115–122. PMID: 6599220.

9. Larsen HC, Angelborg C, Klockoff I, Stahle J. The effect of isosorbide and urea on hearing inpatients with Ménière's disease. Acta Otolaryngol (Stockh) Suppl. 1984; 412:113–114.

10. Yamazaki T, Imoto T, Hayashi N, Watanabe S, Kozaki H, Abe T. Menière's disease and isosorbide as an oral hyperosmotic agent. Arch Otorhinolaryngol. 1982; 234(1):97–104. PMID: 7082223.

11. Nozawa I, Nakayama H, Hashimoto K, Imamura S, Hisamatu K, Murakami Y. Efficacy of long-term administration of isosorbide for Ménière's disease. ORL J Otorhinolaryngol Relat Spec. 1995; May-Jun. 57(3):135–140. PMID: 7603692.

12. Kakigi A, Takeda T, Sawada S, Taguchi D. Antidiuretic hormone and osmolality in isosorbide therapy and glycerol test. ORL J Otorhinolaryngol Relat Spec. 2006; 68(5):279–282. PMID: 16699291.

13. Scheibe F, Haupt H. Biochemical differences between perilymph, cerebrospinal fluid and blood plasma in the guinea pig. Hear Res. 1985; 1. 17(1):61–66. PMID: 3997682.

14. Sajjadi H, Paparella MM. Meniere's disease. Lancet. 2008; 8. 372(9636):406–414. PMID: 18675691.

15. Goycoolea MV, Lundman L. Round window membrane. Structure function and permeability: a review. Microsc Res Tech. 1997; 2. 36(3):201–211. PMID: 9080410.

16. Salt AN, Kellner C, Hale S. Contamination of perilymph sampled from the basal cochlear turn with cerebrospinal fluid. Hear Res. 2003; 8. 182(1-2):24–33. PMID: 12948598.

17. Hahn H, Salt AN, Biegner T, Kammerer B, Delabar U, Hartsock JJ, et al. Dexamethasone levels and base-to-apex concentration gradients in the scala tympani perilymph after intracochlear delivery in the guinea pig. Otol Neurotol. 2012; 6. 33(4):660–665. PMID: 22588238.

18. Iida T, Teranishi M, Yoshida T, Otake H, Sone M, Kato M, et al. Magnetic resonance imaging of the inner ear after both intratympanic and intravenous gadolinium injections. Acta Otolaryngol. 2013; 5. 133(5):434–438. PMID: 23294239.