title: Cochlear pharmacokinetics of cisplatin: an in vivo study in the guinea pig.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  In vivo animal study.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Victoria
authors.initials: V
authors.lastname: Hellberg
authors.forename: Inger
authors.initials: I
authors.lastname: Wallin
authors.forename: Hans
authors.initials: H
authors.lastname: Ehrsson
authors.forename: Göran
authors.initials: G
authors.lastname: Laurell
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D002853:Chromatography, Liquid; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005500:Follow-Up Studies; D006168:Guinea Pigs; D007275:Injections, Intravenous; D010498:Perilymph / Q000187:drug effects / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin
keywords: Ototoxicity; outer hair cells; pharmacokinetics; scala tympani perilymph