Literature DB >> 9807064

Kinetics of gentamicin uptake in the inner ear of Chinchilla langier after middle-ear administration in a sustained-release vehicle.

B J Balough1, M E Hoffer, D Wester, M J O'Leary, C R Brooker, M Goto.   

Abstract

The search for a safe, effective treatment for the vertigo associated with Meniere's disease has long been an important topic in otolaryngology. In recent years many groups have begun using intratympanic gentamicin to treat this vertigo. Although reported cure rates are as high as 90%, many questions remain regarding this type of treatment. Current limitations are the necessity for repeated treatments and a lack of clear dosing guidelines. In addition, the gentamicin must be delivered in a manner that allows maximal vestibulotoxic effect without injury to hearing. Until investigators can control the exact amount of medicine that is placed in the ear and have an understanding of the kinetics of gentamicin absorption, adequate dosing guidelines will be difficult to establish, and therapy will continue to rely on empiric data. We describe the use of a fibrin-based sustained-release vehicle, impregnated with gentamicin, injected into the middle ear of chinchillas. This allows for a prolonged effect without repeated dosing. Using this model, we studied the absorption kinetics of gentamicin at time points ranging from 8 hours to 1 week after injection. We used our findings to create a kinetics curve of gentamicin absorption. We discuss the shape and characteristics of this kinetics curve and examine the effects of the fibrin-based sustained-release vehicle and gentamicin on the middle ear. We noted no absorption in the contralateral (untreated ear) or blood. Through better understanding of the actions of gentamicin in this animal model, we hope to facilitate safer use of intratympanic medicines in our patient population and initiate programs for the use of this sustained-release vehicle in human beings.

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Year:  1998        PMID: 9807064     DOI: 10.1016/S0194-5998(98)70097-X

Source DB:  PubMed          Journal:  Otolaryngol Head Neck Surg        ISSN: 0194-5998            Impact factor:   3.497


  10 in total

Review 1.  Local inner-ear drug delivery and pharmacokinetics.

Authors:  Alec N Salt; Stefan K R Plontke
Journal:  Drug Discov Today       Date:  2005-10-01       Impact factor: 7.851

Review 2.  [Inquiries into local application of drugs on the inner ear. Innovation prize of the Working Group for German Speaking Audiologists and Neuro-otologists 2005].

Authors:  S Plontke
Journal:  HNO       Date:  2005-10       Impact factor: 1.284

3.  Pharmacokinetics of Drug Entry into Cochlear Fluids.

Authors:  Alec N Salt
Journal:  Volta Rev       Date:  2005

4.  Dependence of hearing changes on the dose of intratympanically applied gentamicin: a meta-analysis using mathematical simulations of clinical drug delivery protocols.

Authors:  Alec N Salt; Ruth M Gill; Stefan K Plontke
Journal:  Laryngoscope       Date:  2008-10       Impact factor: 3.325

Review 5.  Delivery of therapeutics to the inner ear: The challenge of the blood-labyrinth barrier.

Authors:  Sophie Nyberg; N Joan Abbott; Xiaorui Shi; Peter S Steyger; Alain Dabdoub
Journal:  Sci Transl Med       Date:  2019-03-06       Impact factor: 17.956

6.  Perilymph pharmacokinetics of locally-applied gentamicin in the guinea pig.

Authors:  A N Salt; J J Hartsock; R M Gill; E King; F B Kraus; S K Plontke
Journal:  Hear Res       Date:  2016-10-08       Impact factor: 3.208

Review 7.  Inner Ear Drug Delivery for Sensorineural Hearing Loss: Current Challenges and Opportunities.

Authors:  Sophie S Liu; Rong Yang
Journal:  Front Neurosci       Date:  2022-05-24       Impact factor: 5.152

8.  Concentration gradient along the scala tympani after local application of gentamicin to the round window membrane.

Authors:  Stefan K Plontke; Robert Mynatt; Ruth M Gill; Stefan Borgmann; Alec N Salt
Journal:  Laryngoscope       Date:  2007-07       Impact factor: 3.325

9.  Novel flower-shaped albumin particles as controlled-release carriers for drugs to penetrate the round-window membrane.

Authors:  Zhan Yu; Min Yu; Zhimin Zhou; Zhibao Zhang; Bo Du; Qingqing Xiong
Journal:  Int J Nanomedicine       Date:  2014-07-01

10.  Bovine serum albumin nanoparticles as controlled release carrier for local drug delivery to the inner ear.

Authors:  Zhan Yu; Min Yu; Zhibao Zhang; Ge Hong; Qingqing Xiong
Journal:  Nanoscale Res Lett       Date:  2014-07-09       Impact factor: 4.703

  10 in total

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