Intratympanic Versus Intravenous Delivery of Methylprednisolone to Cochlear Perilymph

Bird, Philip; Begg, Evan J.; Zhang, Mei; Keast, Allan T.; Murray, D.; Bałkany, Thomas J.

doi:10.1097/mao.0b013e31815aee21

Cited by 194 publications

(181 citation statements)

References 25 publications

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“…Based on our new data, it now appears likely that elimination from perilymph occurs more rapidly than from the middle ear. The high rate of elimination seen here is more compatible with Plontke et al's (2008a) analysis of methylprednisolone data from humans (Bird et al 2007), which suggested an elimination half-time of 27 mins (also based on similar elimination rate from ST and the middle ear). Differences between all these studies could also arise from the fact that different glucocorticoids were used and each could exhibit different kinetics.…”

Section: Discussionsupporting

confidence: 78%

“…There have been numerous pharmacokinetic studies of locally-applied corticosteroids in animals (Nomura 1984;Parnes et al 1999;Chandrasekhar et al 2000;Bachmann et al 2001;Hahn et al 2006Hahn et al , 2012Liu et al 2006;Plontke et al 2008b;Yang et al 2008;Wang et al 2009;Borden et al 2011;Salt et al 2011a) and humans (Bird et al 2007;Bird et al 2011), but only a subset of these studies has been analyzed quantitatively to derive an elimination rate. Plontke and analyzed prednisoline data of Bachmann et al (2001) from guinea pigs and found it to be consistent with an elimination half-time from perilymph of 130 min.…”

Section: Introductionmentioning

confidence: 99%

“…Plontke and analyzed prednisoline data of Bachmann et al (2001) from guinea pigs and found it to be consistent with an elimination half-time from perilymph of 130 min. An analysis of human methylpresnisolone data from Bird et al (2007) by Plontke et al (2008a) suggested an elimination half-time of 27 mins. Following intratympanic applications of dexamethsone in guinea pigs, elimination half-time was estimated to be 85 min for samples taken at 6 h after application and 155 min for samples taken at 24 h after application (Salt et al 2011a).…”

Section: Introductionmentioning

confidence: 99%

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Perilymph Pharmacokinetics of Markers and Dexamethasone Applied and Sampled at the Lateral Semi-Circular Canal

Salt

Hartsock

Gill

et al. 2012

JARO

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Perilymph pharmacokinetics was investigated by a novel approach, in which solutions containing drug or marker were injected from a pipette sealed into the perilymphatic space of the lateral semi-circular canal (LSCC). The cochlear aqueduct provides the outlet for fluid flow so this procedure allows almost the entire perilymph to be exchanged. After wait times of up to 4 h the injection pipette was removed and multiple, sequential samples of perilymph were collected from the LSCC. Fluid efflux at this site results from cerebrospinal fluid (CSF) entry into the basal turn of scala tympani (ST) so the samples allow drug levels from different locations in the ear to be defined. This method allows the rate of elimination of substances from the inner ear to be determined more reliably than with other delivery methods in which drug may only be applied to part of the ear. Results were compared for the markers trimethylphenylammonium (TMPA) and fluorescein and for the drug dexamethasone (Dex). For each substance, the concentration in fluid samples showed a progressive decrease as the delay time between injection and sampling was increased. This is consistent with the elimination of substance from the ear with time. The decline with time was slowest for fluorescein, was fastest for Dex, with TMPA at an intermediate rate. Simulations of the experiments showed that elimination occurred more rapidly from scala tympani (ST) than from scala vestibuli (SV). Calculated elimination half-times from ST averaged 54.1, 24.5 and 22.5 min for fluorescein, TMPA and Dex respectively and from SV 1730, 229 and 111 min respectively. The elimination of Dex from ST occurred considerably faster than previously appreciated. These pharmacokinetic parameters provide an important foundation for understanding of drug treatments of the inner ear.

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Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Perilymph Pharmacokinetics of Markers and Dexamethasone Applied and Sampled at the Lateral Semi-Circular Canal

Salt

Hartsock

Gill

et al. 2012

JARO

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“…Gd remains in the fluid space that it was applied to for 24 h or longer. In contrast, other drugs such as steroids readily enter endolymph (Parnes et al 1999) and are cleared rapidly from the cochlear fluids (Bird et al 2007;Plontke et al 2008). It remains uncertain whether the predominant entry of Gd in the region of the stapes is a general property of the inner ear, or whether this reflects a characteristic specific to Gd, perhaps related to a very low rate of Gd entry through the RW membrane.…”

Section: Discussionmentioning

confidence: 99%

Direct Entry of Gadolinium into the Vestibule Following Intratympanic Applications in Guinea Pigs and the Influence of Cochlear Implantation

King

Salt

Eastwood

et al. 2011

JARO

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Although intratympanic (IT) administration of drugs has gained wide clinical acceptance, the distribution of drugs in the inner ear following IT administration is not well established. Gadolinium (Gd) has been previously used as a marker in conjunction with magnetic resonance imaging (MRI) to visualize distribution in inner ear fluids in a qualitative manner. In the present study, we applied gadolinium chelated with diethylenetriamine penta-acetic acid (Gd-DTPA) to the round window niche of 12 guinea pigs using Seprapack TM (carboxlmethylcellulose--hyaluronic acid) pledgets which stabilized the fluid volume in the round window niche. Gd-DTPA distribution was monitored sequentially with time following application. Distribution in normal, unperforated ears was compared with ears that had undergone a cochleostomy in the basal turn of scala tympani and implantation with a silastic electrode. Results were quantified using image analysis software. In all animals, Gd-DTPA was seen in the lower basal scala tympani (ST), scala vestibuli (SV), and throughout the vestibule and semi-circular canals by 1 h after application. Although Gd-DTPA levels in ST were higher than those in the vestibule in a few ears, the majority showed higher Gd-DTPA levels in the vestibule than ST at both early and later time points. Quantitative computer simulations of the experiment, taking into account the larger volume of the vestibule compared to scala tympani, suggest most Gd-DTPA (up to 90%) entered the vestibule directly in the vicinity of the stapes rather than indirectly through the round window membrane and ST. Gd-DTPA levels were minimally affected by the implantation procedure after 1 h. Gd-DTPA levels in the basal turn of scala tympani were lower in implanted animals, but the difference compared to non-implanted ears did not reach statistical significance.

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“…Intratympanic (IT) treatment options are good alternatives in patients that do not respond to medical treatment. It has been shown that medications administered into the middle ear pass into the inner ear through oval and round windows, in very high concentrations [2] . IT gentamicin application has been widely accepted in Meniere's disease because of the dominant vestibulotoxic effect of the agent [3,4] .…”

Section: Introductionmentioning

confidence: 99%

Selective Window Application of Gentamicin Dexamethasone in Meniere's Disease

Ardıç

Tümkaya²,

Aykal³

et al. 2017

Int Adv Otol

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OBJECTIVE:The purpose of the study is to prevent hearing loss when using intratympanic (IT) gentamicin for intractable Meniere's disease. MATERIALS and METHODS:It is a retrospective case review study. Twenty five patients who had definite Meniere's disease and had either selective window application or weekly IT gentamicin were included into the study. First group (selective) had dexamethasone on the round window and gentamicin on oval window during exploratory tympanotomy procedure. The second group had IT gentamicin at weekly intervals. The degree of caloric weakness (CW), average hearing level in low pitch (HLP) (250, 500, 1000, 2000 Hz) and high pitch (HHP) (4000, 6000, 8000 Hz) were compared before and after treatment. The need for further treatment was noted. RESULTS:In the first group, the average HLP was increased from 51.6±7dB to 52.2±5.6 dB. The average HHP was increased 41.96±20.2 dB to 47.2±18.3 dB after treatment. The CW changed from 37.6±23.9 % to 54.6±30.6 %. In the second group, the average HLP was increased from 56.3±10.5 dB to 61.65±18.3 dB. The average HHP was increased 59.05±17.4 dB to 69.4±21.98 dB after treatment. The CW changed from 45.8±22.3% to 71.53±29.63 %. Both methods had statisticaly significant increase in caloric weakness. But only IT gentamicin led a significant hearing loss in HHP. CONCLUSION:The use of dexamethasone and gentamycin via different windows in the middle ear is safe and effective method for Meniere's disease in the short term. Application of dexamethasone protects not only the hearing cells but vestibular cells also.

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Intratympanic Versus Intravenous Delivery of Methylprednisolone to Cochlear Perilymph

Abstract: IT administration of methylprednisolone in humans results in much higher perilymph concentrations and much lower systemic concentrations than IV administration.

Cited by 194 publications

References 25 publications

Perilymph Pharmacokinetics of Markers and Dexamethasone Applied and Sampled at the Lateral Semi-Circular Canal

Perilymph Pharmacokinetics of Markers and Dexamethasone Applied and Sampled at the Lateral Semi-Circular Canal

Direct Entry of Gadolinium into the Vestibule Following Intratympanic Applications in Guinea Pigs and the Influence of Cochlear Implantation

Selective Window Application of Gentamicin Dexamethasone in Meniere's Disease

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