PMID- 22588238
OWN - NLM
STAT- MEDLINE
DCOM- 20120927
LR  - 20220331
IS  - 1537-4505 (Electronic)
IS  - 1531-7129 (Print)
IS  - 1531-7129 (Linking)
VI  - 33
IP  - 4
DP  - 2012 Jun
TI  - Dexamethasone levels and base-to-apex concentration gradients in the scala 
      tympani perilymph after intracochlear delivery in the guinea pig.
PG  - 660-5
LID - 10.1097/MAO.0b013e318254501b [doi]
AB  - HYPOTHESIS: To determine whether intracochlearly applied dexamethasone will lead 
      to better control of drug levels, higher peak concentrations, and lower 
      base-to-apex concentration gradients in the scala tympani (ST) of the guinea pig 
      than after intratympanic (round window [RW]) application. BACKGROUND: Local 
      application of drugs to the RW results in substantial variation of intracochlear 
      drug levels and significant base-to-apex concentration gradients in ST. METHODS: 
      Two microliters of dexamethasone-phosphate (10 mg/ml) were injected into ST 
      either through the RW membrane, which was covered with 1% sodium hyaluronate gel 
      or through a cochleostomy with a fluid tight seal of the micropipette. Perilymph 
      was sequentially sampled from the apex at a single time point for each animal, at 
      20, 80, or 200 min after the injection ended. Results were mathematically 
      interpreted by means of an established computer model and compared with previous 
      experiments performed by our group with the same experimental techniques but 
      using intratympanic applications. RESULTS: Single intracochlear injections of 20 
      minutes resulted in approximately 10 times higher peak concentrations (on 
      average) than 2 to 3 hours of intratympanic application to the RW niche. 
      Intracochlear drug levels were less variable and could be measured for over 220 
      minutes. Concentration gradients along the scala tympani were less pronounced. 
      The remaining variability in intracochlear drug levels was attributable to 
      perilymph and drug leak from the injection site. CONCLUSION: With significantly 
      higher, less variable drug levels and smaller base-to-apex concentration 
      gradients, intracochlear applications have advantages to intratympanic 
      injections. For further development of this technique, it is of importance to 
      control leaks of perilymph and drug from the injection site and to evaluate its 
      clinical feasibility and associated risks.
FAU - Hahn, Hartmut
AU  - Hahn H
AD  - Department of Otorhinolaryngology-Head and Neck Surgery and Tubingen Hearing 
      Research Center, University of Tubingen, Tubingen, Germany.
FAU - Salt, Alec N
AU  - Salt AN
FAU - Biegner, Thorsten
AU  - Biegner T
FAU - Kammerer, Bernd
AU  - Kammerer B
FAU - Delabar, Ursular
AU  - Delabar U
FAU - Hartsock, Jared J
AU  - Hartsock JJ
FAU - Plontke, Stefan K
AU  - Plontke SK
LA  - eng
GR  - R01 DC001368/DC/NIDCD NIH HHS/United States
GR  - DC01368/DC/NIDCD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Otol Neurotol
JT  - Otology & neurotology : official publication of the American Otological Society, 
      American Neurotology Society [and] European Academy of Otology and Neurotology
JID - 100961504
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Animals
MH  - Dexamethasone/administration & dosage/*pharmacokinetics
MH  - Guinea Pigs
MH  - Injections
MH  - Models, Biological
MH  - Perilymph/metabolism
MH  - Round Window, Ear/*metabolism
MH  - Scala Tympani/*metabolism
MH  - Time Factors
PMC - PMC3354992
MID - NIHMS369165
EDAT- 2012/05/17 06:00
MHDA- 2012/09/28 06:00
PMCR- 2013/06/01
CRDT- 2012/05/17 06:00
PHST- 2012/05/17 06:00 [entrez]
PHST- 2012/05/17 06:00 [pubmed]
PHST- 2012/09/28 06:00 [medline]
PHST- 2013/06/01 00:00 [pmc-release]
AID - 00129492-201206000-00031 [pii]
AID - 10.1097/MAO.0b013e318254501b [doi]
PST - ppublish
SO  - Otol Neurotol. 2012 Jun;33(4):660-5. doi: 10.1097/MAO.0b013e318254501b.