The pharmacokinetic profiles of dexamethasone and methylprednisolone concentration in perilymph and plasma following systemic and local administration

Yang, Jun; Wu, Hao; Zhang, Ping; Hou, Dongming; Chen, Jie; Zhang, Shunguo

doi:10.1080/00016480701558906

Cited by 50 publications

(38 citation statements)

References 29 publications

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“…Pharmacokinetic studies conducted by several investigators suggest that the duration and degree of inner ear exposure following topical application of dexamethasone is relatively similar to that of other steroids such as methylprednisolone and hydrocortisone [Li et al, 2005;Parnes et al, 1999;Yang et al, 2008]. In addition, the high affinity of dexamethasone for its targets (glucocorticoid and mineralocorticoid receptors) [Grossmann et al, 2004] constitutes another attractive property that led to the selection of dexamethasone in this study, as opposed to other steroids.…”

Section: Introductionmentioning

confidence: 98%

Pharmacokinetics of Dexamethasone Solution following Intratympanic Injection in Guinea Pig and Sheep

et al. 2010

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Information on inner ear pharmacokinetics is limited in the literature, especially in large animals and in humans. A preliminary study was designed to explore the differences in inner ear exposure between guinea pigs and sheep following a single intratympanic injection of a 2% dexamethasone sodium phosphate solution. In both species, significant levels of dexamethasone were observed in the perilymph within 1 h, and decreasing by 50- to 100-fold within 12 h. Overall, the exposure to dexamethasone in the inner ear was significantly lower in sheep by 17- to 27-fold than in guinea pigs. Systemic and CNS exposure were minimal in both species as indicated by the low drug levels observed in plasma and CSF. Altogether, the preliminary evidence presented herein suggests the sheep as a practical and acceptable animal model to study the inner ear pharmacokinetics of drug candidates in large mammals and its potential towards extrapolation to human exposure.

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Section: Introductionmentioning

confidence: 98%

Pharmacokinetics of Dexamethasone Solution following Intratympanic Injection in Guinea Pig and Sheep

et al. 2010

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“…Moreover, ITMP is well tolerated and safe, without the adverse effects of systemic steroids, and it increases the amount of steroids entering the inner ear when compared with systemic routes of administration [18,34] .…”

Section: Discussionmentioning

confidence: 99%

“…These anomalies might correspond to really ductal narrowness or to plugs of otoconial debris [11,12] . Preliminary reports about these labyrinth abnormalities led us to consider the use of steroids because of their anti-inflammatory effect since glucocorticoid receptors are prevalent throughout the inner ear, including the vestibular structures (such as maculae of the utricle and saccule, otoconial membrane, the semicircular canal cristae, semicircular canal duct epithelium, and extramacular epithelium of the saccule) [15,18] . If the BPPV persistence had an inflammatory origin, the steroids can assist in improving the success of the maneuvers.…”

Section: Discussionmentioning

confidence: 99%

A Pilot Study Using Intratympanic Methylprednisolone for Treatment of Persistent Posterior Canal Benign Paroxysmal Positional Vertigo

Pérez¹,

Franco²,

Oliva³

et al. 2016

Int Adv Otol

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OBJECTIVE:To assess the effect of intratympanic methylprednisolone (ITMP) in posterior canal benign paroxysmal positional vertigo (BPPV) that fails treatment involving repositioning maneuver in a case series. MATERIALS and METHODS:Nine patients with persistent posterior canal BPPV after 6 or more repositioning maneuvers were treated by ITMP (two weekly doses of 0.3-0.4 mL at 40 mg/mL) before repeating the repositioning procedures. RESULTS:Following ITMP treatment, 7 out of 9 patients were relieved of their symptoms and did not exhibit positional nystagmus after 1 or 2 repositioning maneuvers. The number of positional maneuvers performed before and after ITMP treatment in these 7 patients showed a statistically significant (p=0.016) reduction in the amount of repositioning treatments required. None of the 7 respondent patients showed any relapses during the follow-up period (follow-up range: 11-95 months). CONCLUSION:Administering ITMP before resuming repositioning procedures can be a useful treatment for persistent BPPV of the posterior canal. Intratympanic (IT) steroids are often used to treat inner ear disorders such as sudden idiopathic sensorineural hearing loss, autoimmune hearing loss, and Ménière's disease [14] . Corticosteroids exert their effects in the inner ear after interacting with intracellular glucocorticoid receptors by producing metabolic and anti-inflammatory effects. It is also known that glucocorticoid receptors are widespread throughout the inner ear, including semicircular canal duct epithelial cells, where they facilitate cation absorption via sodium channels [15][16][17] . KEYWORDS:Thus, considering the possibility of an inflammatory process of the labyrinth or an imbalance of Na + and Ca 2+ in the endolymph could be related with the intractability of BPPV, we have carried out a pilot study to assess the effect of IT methylprednisolone (ITMP) in persistent posterior canal BPPV. MATERIALS and METHODSThis prospective study included patients from 3 different hospitals. From January 2006 to March 2014, we diagnosed 187 patients affected from unilateral posterior canal BPPV. None of them had any symptoms or signs of central nervous system (CNS) disease. A complete otoneurological examination, including otoscopy, audiometry, head thrust test, spontaneous nystagmus recording, gaze-evoked nystagmus test, cover test, and Romberg and Fukuda tests, were performed in all the cases.The diagnosis of posterior canal BPPV was made by Dix-Hallpike test, showing a mixed vertical and torsional nystagmus beating toward the undermost ear, with appropriate latency and duration, and the direction of the nystagmus reversed on resuming the upright position. In every patient, the roll test and head hyperextension test were also performed in order to rule out lateral or superior canal BPPV.Patients with BPPV were treated by Epley or Semont maneuvers. We carried out only one of those maneuvers in every session. Each session, weekly programmed, began with a Dix-Hallpike test; if it was positive for the same posterior...

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“…Methylprednisolone and dexamethasone are the most widely used agents for the intratympanic administration protocols [5].…”

Section: Introductionmentioning

confidence: 99%

Recovery of Hearing in Cisplatin-Induced Ototoxicity in the Guinea Pig with Intratympanic Dexamethasone

Çallı¹,

Pınar²,

Öncel³

et al. 2011

Indian J Otolaryngol Head Neck Surg

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The purpose of this study was to investigate the effectiveness of intratympanic dexamethasone injection as a therapeutic agent against cisplatin-induced ototoxicity. Animals were randomly divided into three groups. Group one received intraperitoneal cisplatin alone, group two, received intratympanic dexamethasone after cisplatin ototoxicity had been demonstrated. Group three, which is control group, received intratympanic dexamethasone.Then we made three measurements. First we measured the baseline distortion product otoacustic emission (DPOAEs) of all the guine pigs. Second we injected cisplatin intraperitoneal group one and two the same day. Third we measured DPOAEs after 72 h of group one and two. Moreover DPOAEs were measured at the end of the first and second week only in group two. Cochleae were harvested and processed for electron microscopy after then. Values of The DPOAEs amplitudes and signal-to-noise ratio (SNR) at 1-6 kHz frequencies for group 1 after the injections significantly decreased over those before injections (P \ 0.05). In group 3, there were no significant differences in DPOAE amplitude and SNR values When they are compare before and after their intratympanic dexamethasone injections (P [ 0.05). In group 2, the DPOAEs measurements were close to significance at the end of the second week (P = 0.056). Intratympanic dexamethasone injection did not cause any ototoxic effect. Although intratympanic dexamethasone did not reach the statistically significant results, the measurements were close to significance. Intratympanic dexamethasone might have a significant therapeutic effect after cisplatin ototoxicity with different dose and application regimens.

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The pharmacokinetic profiles of dexamethasone and methylprednisolone concentration in perilymph and plasma following systemic and local administration

Cited by 50 publications

References 29 publications

Pharmacokinetics of Dexamethasone Solution following Intratympanic Injection in Guinea Pig and Sheep

Pharmacokinetics of Dexamethasone Solution following Intratympanic Injection in Guinea Pig and Sheep

A Pilot Study Using Intratympanic Methylprednisolone for Treatment of Persistent Posterior Canal Benign Paroxysmal Positional Vertigo

Recovery of Hearing in Cisplatin-Induced Ototoxicity in the Guinea Pig with Intratympanic Dexamethasone

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