This work was supported by AFA Insurance, Foundation Tysta Skolan, and Acta Oto-Laryngologica. Training of the surgical procedure and protocol for sampling of ST perilymph from apex was kindly provided by Professor Alec N. Salt, Washington University, St. Louis, U.S.A. The authors have no other funding, financial relationships, or conflicts of interest to disclose.
Cochlear pharmacokinetics of cisplatin: An in vivo study in the guinea pig
Article first published online: 29 JUL 2013
Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.
Volume 123, Issue 12, pages 3172–3177, December 2013
How to Cite
Hellberg, V., Wallin, I., Ehrsson, H. and Laurell, G. (2013), Cochlear pharmacokinetics of cisplatin: An in vivo study in the guinea pig. The Laryngoscope, 123: 3172–3177. doi: 10.1002/lary.24235
- Issue published online: 25 NOV 2013
- Article first published online: 29 JUL 2013
- Accepted manuscript online: 11 JUN 2013 03:56AM EST
- Manuscript Revised: 14 MAY 2013
- Manuscript Accepted: 14 MAY 2013
- scala tympani perilymph;
- outer hair cells
Cisplatin produces toxic lesions to outer hair cells (OHCs) in the cochlear base but not in the apex. The objective of this study was to compare the pharmacokinetic profile of cisplatin in scala tympani (ST) perilymph in the cochlear base and apex, respectively.
In vivo animal study.
Forty-seven guinea pigs were given an intravenous bolus injection of an ototoxic dose of cisplatin. Ten to 240 minutes after cisplatin was given, blood, cerebrospinal fluid (CSF), and ST perilymph were aspirated within the same target time. ST perilymph was aspirated from the basal turn and from the apex of the cochlea by two different sampling techniques. Liquid chromatography with postcolumn derivatization was used for quantitative determination of the parent drug.
Ten minutes after administration, the concentration of cisplatin in ST perilymph was 4-fold higher in the basal turn of the cochlea than in the apex. At 30 minutes, the drug concentrations did not differ. At 60 minutes, the level of cisplatin in ST perilymph and blood UF was equivalent. The perilymph-blood ratio increased thereafter with time.
The pharmacokinetic findings of an early high concentration of cisplatin in the base of the cochlea and delayed elimination of cisplatin from ST perilymph compared to blood might correlate to the cisplatin-induced loss of OHCs in the base of the cochlea.
Level of Evidence
N/A. Laryngoscope, 123:3172–3177, 2013