Cochlear Mechanics and Otoacoustic Emissions

Local, rather than systemic, drug delivery to the inner ear is becoming more widely used to treat inner ear disorders. While many substances are undergoing preclinical and clinical studies, it is equally important to develop appropriate drug delivery systems. Pharmacokinetic studies are technically demanding in animals and almost impossible in humans. Computer simulations have helped establish the basic principles of drug distribution in the inner ear. The distribution of methylprednisolone in the guinea pig cochlea has been simulated for different drug delivery systems based on kinetic parameters established in prior studies. Results were compared for different rates of drug clearance from the middle ear. Absolute and relative drug levels in the perilymph were highly dependent on how long the drug remained in the middle ear. For a brief (30 min) application, the basal to apical drug gradient was higher than for longer delivery times. These findings show that controlling middle ear drug clearance is of critical importance. Copyright © 2006 S. Karger AG, Basel Published online: October 26, 2006 Dr. Stefan Plontke, Department of Otorhinolaryngology Head and Neck Surgery, University of Tübingen Elfriede-Aulhorn-Strasse 5, DE–72076 Tübingen (Germany) Tel. +49 7071 29 88088, Fax +49 7071 29 3311 E-Mail [email protected] © 2006 S. Karger AG, Basel Accessible online at: www.karger.com/orl Inner Ear Drug Delivery Systems and Pharmacokinetics ORL 2006;68:386–392 387 Fig. 1. Application systems for local drug delivery to the inner ear. a Intratympanic injection. b Microotoscope ‘Model Tübingen’, GYRUS Medical GmbH (former Explorent /STUEMED ): outer diameter: 1.2 mm; including an optical channel (0.5 mm) with 6,000 fibers and two working or suction channels (0.27 and 0.3 mm), which may be used for targeted intratympanic drug delivery after visualization of the round window niche (from Plontke et al. [27] , with permission of S. Karger AG, 2002). c Silverstein Micro Wick TM [8] , printed with permission of Micromedics Inc., St. Paul, Minn., USA. d Totally implantable drug delivery system [14, 28] (printed with permission of R. Lehner and H.P. Zenner, Germany). e Temporarily implantable catheter approved for intratympanic drug delivery ‘Arenberg catheter’ (RW /ECath TM , printed with permission of DURECT TM , Cupertino, Calif., USA). f Poly-lactic/glycolic acid nanoparticles (arrow) loaded with rhodamine entering the scala tympani after placement at the RWM of the guinea pig (from Tamura et al. [11] , with permission of Lippincott Williams & Wilkins, 2005). * = Scala tympani.