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Cochlear Pharmacokinetics of Cisplatin: An In Vivo Study in the Guinea Pig
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
2013 (English)In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 123, no 12, 3172-3177 p.Article in journal (Refereed) Published
Abstract [en]

Objectives/HypothesisCisplatin 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. Study DesignIn vivo animal study. MethodsForty-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. ResultsTen 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. ConclusionThe 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 EvidenceN/A. Laryngoscope, 123:3172-3177, 2013

Place, publisher, year, edition, pages
2013. Vol. 123, no 12, 3172-3177 p.
Keyword [en]
Ototoxicity, pharmacokinetics, scala tympani perilymph, outer hair cells
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-213479DOI: 10.1002/lary.24235ISI: 000327310500066OAI: oai:DiVA.org:uu-213479DiVA: diva2:682896
Available from: 2013-12-30 Created: 2013-12-23 Last updated: 2013-12-30Bibliographically approved

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