Treatment of Vestibular Disorders

Itoh, Akinori; Sakata, Eiji

doi:10.3109/00016489109131486

Cited by 106 publications

(84 citation statements)

References 6 publications

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“…Gentamicin is toxic to the sensory cells of the balance system and thereby suppresses the vertigo in these patients by partially ablating their vestibular system. There are also an increasing number of clinical reports related to the local application of glucocorticoids for acute hearing loss (9,10,11,12,13,14,15,16), glucocorticoids for Menière's disease (17,18,19,20) or for tinnitus (21,22,23,24,25). Other substances that have been tested in humans include local anaesthetics, neurotransmitters and neurotransmitter antagonists (26,27).…”

Section: Introductionmentioning

confidence: 99%

Local inner-ear drug delivery and pharmacokinetics

Salt

Plontke

2005

Drug Discovery Today

163

123

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SummaryA number of drugs are in widespread clinical use for the treatment of inner ear disorders by applying them directly to the inner ear. Many new substances and drug delivery systems specific to the inner ear are under development, and in some cases are undergoing evaluations in animal experiments and in clinical studies. The pharmacokinetics of drugs in the inner ear, however, is not well defined and the field is plagued by technical problems in obtaining pure samples of the inner ear fluids for analysis. Nevertheless, a basic understanding of the mechanisms of drug dispersal in the inner ear has emerged that facilitates the design and interpretation of future pharmacokinetic studies.

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Section: Introductionmentioning

confidence: 99%

Local inner-ear drug delivery and pharmacokinetics

Salt

Plontke

2005

Drug Discovery Today

163

123

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“…There are a growing number of clinical reports with regard to local treatments with corticosteroids in cases of acute hearing loss of various causes (Chandrasekhar, 2001;Gian-oli and Li, 2001;Gouveris et al, 2005;Ho et al, 2004;Lautermann et al, 2005;Lefebvre and Staecker, 2002;Plontke et al, 2005;Silverstein et al, 1996;Parnes et al, 1999), of Meniere's disease (Itoh and Sakata, 1991;Sennaroglu et al, 2001;Shea and Ge, 1996;Silverstein et al, 1998) and of tinnitus (Cesarani et al, 2002;Coles et al, 1992;Sakata et al, 1997;Shulman and Goldstein, 2000;Silverstein et al, 1996). In addition, a number of investigational drugs show promising results with respect to protection when locally applied to the RWM Chen et al, 2003b;Hight et al, 2003;Keithley et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Cochlear microdialysis for quantification of dexamethasone and fluorescein entry into scala tympani during round window administration

et al. 2006

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Before new drugs for the treatment of inner ear disorders can be studied in controlled clinical trials, it is important that their pharmacokinetics be established in inner ear fluids. Microdialysis allows drug levels to be measured in perilymph without the volume disturbances and potential cerebrospinal fluid contamination associated with fluid sampling. The aims of this study were to show: (i) that despite low recovery rates from miniature dialysis probes, significant amounts of drug are removed from small fluid compartments, (ii) that dialysis sampling artifacts can be accounted for using computer simulations and (iii) that microdialysis allows quantification of the entry rates through the round window membrane (RWM) into scala tympani (ST). Initial experiments used microdialysis probes in small compartments in vitro containing sodium fluorescein. Stable concentrations were observed in large compartments (1000 μl) but significant concentration declines were observed in smaller compartments (100, 10 and 5.6 μl) comparable to the size of the inner ear. Computer simulations of these experiments closely approximated the experimental data. In in vivo experiments, sodium fluorescein 10 mg/ml and dexamethasone-dihydrogen-phosphate disodium salt 8 mg/ml were simultaneously applied to the RWM of guinea pigs. Perilymph concentration in the basal turn of ST was monitored using microdialysis. The fluorescein concentration reached after 200 min application (585 ± 527 μg/ml) was approximately twice that of dexamethasone phosphate (291 ± 369 μg/ml). Substantial variation in concentrations was found between animals by approximately a factor of 34 for fluorescein and at least 41 for dexamethasone phosphate. This is, to a large extent, thought to be the result of the RWM permeability varying in different animals. It was not caused by substance analysis variations, because two different analytic methods were used and the concentration ratio between the two substances remained nearly constant across the experiments and because differences were apparent for the repeated samples obtained in each animal. Interpretation of the results using computer simulations allowed RWM permeability to be quantified. It also demonstrated, however, that cochlear clearance values could not be reliably obtained with microdialysis because of the significant contribution of dialysis to clearance. The observed interanimal variation, e.g., in RWM permeability, is likely to be clinically relevant to the local application of drugs in patients.

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“…One of the first reports regarding the effects of IT steroids for Ménière's disease showed 80% improvement in vertigo and a 74% reduction in tinnitus in 61 patients (7). The use of IT and intravenous corticosteroids showed short-term control of vertigo in 96.4% and an improvement in hearing loss in 67.9% of 28 patients in Shea's stages I to III of Ménière's disease (8).…”

mentioning

confidence: 99%

Longitudinal Results With Intratympanic Dexamethasone in the Treatment of Ménière's Disease

Boleas-Aguirre

Lin²,

Santina³

et al. 2008

Otology &Amp; Neurotology

107

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Objective-To assess patient satisfaction with vertigo control using intratympanic (IT) dexamethasone (12 mg/mL) for medically refractory unilateral Ménière's disease.Study Design-Retrospective study. Setting-Tertiary referral neurotology clinic.Patients-One hundred twenty-nine subjects diagnosed with unilateral Ménière's disease still having vertigo despite medical therapy. Intervention-IT dexamethasone injections as needed to control vertigo attacks.Main Outcome Measure-A Kaplan-Meier time-to-event method was used to determine the rate of "survival," meaning sufficient satisfaction with vertigo control that the subject did not wish to have subsequent ablative treatment. "Failure" was defined as poor control and the choice to proceed to ablative treatment.Results-Acceptable vertigo control ("survival") was achieved in 117 (91%) of 129 subjects. Vertigo control required only one dexamethasone injection in 48 (37%), 2 injections in 26 (20%), 3 injections in 18 (14%), and 4 injections in 10 (8%). More than 4 injections were needed in 15 subjects (21%). Of 12 failures (9%), 9 occurred within 6 months of the first IT dexamethasone injection. Follow-up data for 2 years were available for 96 subjects. Of these, 87 (91%) had vertigo control with IT dexamethasone, of whom 61 (70)% required no further injections after 2 years, 23 (26%) continued to receive IT dexamethasone injections, and 3 (3%) chose IT gentamicin treatment.Conclusion-IT dexamethasone injection therapy on an as-needed outpatient basis can provide vertigo control that is satisfactory in patients with Ménière's disease. The Kaplan-Meier method addresses the need for an outcome measure suited to repeated treatments and variable lengths of follow-up. However, due to the retrospective nature of this study, the presence of bias caused by loss of subjects from follow-up cannot be ruled out.

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Treatment of Vestibular Disorders

Cited by 106 publications

References 6 publications

Local inner-ear drug delivery and pharmacokinetics

Local inner-ear drug delivery and pharmacokinetics

Cochlear microdialysis for quantification of dexamethasone and fluorescein entry into scala tympani during round window administration

Longitudinal Results With Intratympanic Dexamethasone in the Treatment of Ménière's Disease

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