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Intratympanic Versus Intravenous Delivery of Dexamethasone and Dexamethasone Sodium Phosphate to Cochlear Perilymph

Bird, Philip A.*†; Murray, Daran P.*; Zhang, Mei; Begg, Evan J.

doi: 10.1097/MAO.0b013e3182255933
Sensorineural Hearing Loss and Tinnitus
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Objective: To measure dexamethasone concentrations in the plasma and perilymph of the human ear after intravenous (IV) and intratympanic (IT) administration and to compare these with previous studies with methylprednisolone.

Methods: Patients were administered dexamethasone by the IT or IV routes approximately 0.5 to 2 hours before cochlear implantation. The IT dose of 1.6 to 7.2 mg (0.4-1.8 ml of a 4 mg/ml solution) of dexamethasone sodium phosphate was administered by injection into the middle ear cavity through the external auditory canal via a 27-gauge needle passed through a small anterosuperior myringotomy. The IV dose of dexamethasone sodium phosphate was 0.17 mg/kg given as a single injection for 30 seconds. A sample of perilymph (approximately 20 μl) was collected using a needle passed through the round window, and blood was sampled simultaneously. Concentrations of free dexamethasone and dexamethasone sodium phosphate were measured using a validated liquid chromatography-tandem mass spectrometry method.

Results: In the 22 patients studied, 22 perilymph samples and 19 plasma samples were available and suitable for measurement. The median perilymph concentration of dexamethasone after IV injection of 0.17 mg/kg was 0.016 mg/L (n = 9; range, 0.008-0.17), and 1.4 mg/L (n = 13; range, 0.1-16.3) after IT administration of approximately 4 mg. Perilymph concentrations were approximately 88-fold higher after IT compared with IV administration (p = 0.0004) or approximately 260 fold after correction for dosage. The median plasma concentration of dexamethasone after IV injection was 0.12 mg/L (n = 7; range, 0.07-0.14) and 0.003 mg/L (n = 12; range, <0.0005-0.005) after IT injection. Plasma concentrations were approximately 40-fold lower (p = 0.0005) or approximately 13-fold lower after dose correction. Concentrations of dexamethasone sodium phosphate were more variable and were even higher in perilymph and lower in plasma.

Conclusion: Administration of dexamethasone IT results in much higher perilymph concentrations and much lower plasma concentrations compared with IV administration.

*Department of Otolaryngology-Head and Neck Surgery, Christchurch Hospital; and †Departments of Surgery, and ‡Medicine, University of Otago Christchurch, Christchurch, New Zealand

Address correspondence and reprint requests to Philip A. Bird, M.B., Ch.B., F.R.A.C.S., Department of Otolaryngology-Head and Neck Surgery, Christchurch Hospital, Private Bag 4710, Christchurch 8140, New Zealand; E-mail: phil.bird@chchorl.co.nz

© 2011 Otology & Neurotology, Inc.