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Dexamethasone concentration gradients along scala tympani after application to the round window membrane.
Otol Neurotol. 2008 Apr; 29(3):401-6.ON

Abstract

HYPOTHESIS

Local application of dexamethasone-21-dihydrogen-phosphate (Dex-P) to the round window (RW) membrane of guinea pigs produces a substantial basal-apical concentration gradient in scala tympani (ST) perilymph.

BACKGROUND

In recent years, intratympanically applied glucocorticoids are increasingly being used for the treatment of inner ear disease. Although measurements of intracochlear concentrations after RW application exist, there is limited information on the distribution of these drugs in the inner ear fluids. It has been predicted from computer simulations that substantial concentration gradients will occur after RW application, with lower concentrations expected in apical turns. Concentration gradients of other substances along the cochlea have recently been confirmed using a sequential apical sampling method to obtain perilymph.

METHODS

Dexamethasone-21-dihydrogen-phosphate (10 mg/ml) was administered to the RW membrane of guinea pigs (n = 9) in vivo for 2 to 3 hours. Perilymph was then collected using a protocol in which 10 samples, each of approximately 1 mul, were taken sequentially from the cochlear apex into capillary tubes. Dexamethasone-21-dihydrogen-phosphate concentration of the samples was analyzed by high-performance liquid chromatography. Interpretation of sample data using a finite element model allowed the longitudinal gradients of Dex-P in ST to be quantified.

RESULTS

The Dex-P content of the first sample in each experiment (dominated by perilymph from apical regions) was substantially lower than that of the third and fourth sample (dominated by basal turn perilymph). These findings qualitatively demonstrated the existence of a concentration gradient along ST. After detailed analysis of the measured sample concentrations using an established finite element computer model, the mean basal-apical concentration gradient was estimated to be 17,000. Both absolute concentrations of Dex-P in ST and the basal-apical gradients were found to vary substantially.

CONCLUSION

The existence of substantial basal-apical concentration gradients of Dex-P in ST perilymph were demonstrated experimentally. If the variability in peak concentration and gradient is also present under clinical conditions, this may contribute to the heterogeneity of outcome that is observed after intratympanic application of glucocorticoids for various inner ear diseases.

Authors+Show Affiliations

Department of Otorhinolaryngology, Head and Neck Surgery, Tübingen Hearing Research Center, University of Tübingen, Tübingen, Germany. Stefan.Plontke@uni-tuebingen.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18277312

Citation

Plontke, Stefan K., et al. "Dexamethasone Concentration Gradients Along Scala Tympani After Application to the Round Window Membrane." Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, vol. 29, no. 3, 2008, pp. 401-6.
Plontke SK, Biegner T, Kammerer B, et al. Dexamethasone concentration gradients along scala tympani after application to the round window membrane. Otol Neurotol. 2008;29(3):401-6.
Plontke, S. K., Biegner, T., Kammerer, B., Delabar, U., & Salt, A. N. (2008). Dexamethasone concentration gradients along scala tympani after application to the round window membrane. Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 29(3), 401-6. https://doi.org/10.1097/MAO.0b013e318161aaae
Plontke SK, et al. Dexamethasone Concentration Gradients Along Scala Tympani After Application to the Round Window Membrane. Otol Neurotol. 2008;29(3):401-6. PubMed PMID: 18277312.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dexamethasone concentration gradients along scala tympani after application to the round window membrane. AU - Plontke,Stefan K, AU - Biegner,Thorsten, AU - Kammerer,Bernd, AU - Delabar,Ursular, AU - Salt,Alec N, PY - 2008/2/16/pubmed PY - 2008/7/9/medline PY - 2008/2/16/entrez SP - 401 EP - 6 JF - Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology JO - Otol Neurotol VL - 29 IS - 3 N2 - HYPOTHESIS: Local application of dexamethasone-21-dihydrogen-phosphate (Dex-P) to the round window (RW) membrane of guinea pigs produces a substantial basal-apical concentration gradient in scala tympani (ST) perilymph. BACKGROUND: In recent years, intratympanically applied glucocorticoids are increasingly being used for the treatment of inner ear disease. Although measurements of intracochlear concentrations after RW application exist, there is limited information on the distribution of these drugs in the inner ear fluids. It has been predicted from computer simulations that substantial concentration gradients will occur after RW application, with lower concentrations expected in apical turns. Concentration gradients of other substances along the cochlea have recently been confirmed using a sequential apical sampling method to obtain perilymph. METHODS: Dexamethasone-21-dihydrogen-phosphate (10 mg/ml) was administered to the RW membrane of guinea pigs (n = 9) in vivo for 2 to 3 hours. Perilymph was then collected using a protocol in which 10 samples, each of approximately 1 mul, were taken sequentially from the cochlear apex into capillary tubes. Dexamethasone-21-dihydrogen-phosphate concentration of the samples was analyzed by high-performance liquid chromatography. Interpretation of sample data using a finite element model allowed the longitudinal gradients of Dex-P in ST to be quantified. RESULTS: The Dex-P content of the first sample in each experiment (dominated by perilymph from apical regions) was substantially lower than that of the third and fourth sample (dominated by basal turn perilymph). These findings qualitatively demonstrated the existence of a concentration gradient along ST. After detailed analysis of the measured sample concentrations using an established finite element computer model, the mean basal-apical concentration gradient was estimated to be 17,000. Both absolute concentrations of Dex-P in ST and the basal-apical gradients were found to vary substantially. CONCLUSION: The existence of substantial basal-apical concentration gradients of Dex-P in ST perilymph were demonstrated experimentally. If the variability in peak concentration and gradient is also present under clinical conditions, this may contribute to the heterogeneity of outcome that is observed after intratympanic application of glucocorticoids for various inner ear diseases. SN - 1531-7129 UR - https://www.unboundmedicine.com/medline/citation/18277312/Dexamethasone_concentration_gradients_along_scala_tympani_after_application_to_the_round_window_membrane_ L2 - https://doi.org/10.1097/MAO.0b013e318161aaae DB - PRIME DP - Unbound Medicine ER -