Cisplatin-induced ototoxicity and pharmacokinetics: preliminary findings in a dog model.
The early effects of a clinical dose of cisplatin (100 mg/m2) on distortion-product otoacoustic emissions (DPOAE) thresholds and the relationship between DPOAE threshold shifts and changes in plasma concentrations of filterable and total platinum (Pt) following infusion of cisplatin in a dog model were investigated. The DPOAE thresholds (based on input-output function) were measured 2 days before a single high dose of cisplatin administration, and compared with measurements recorded 2 and 4 days after infusion. The results revealed DPOAE thresholds to be elevated by 4 days after the administration of cisplatin. However, this elevation could not be correlated with plasma concentrations of filterable and total Pt, which showed little variation over the 48-hour postinfusion period between animals. The present study demonstrated that DPOAE thresholds have the potential to be used as an indicator of cisplatin-induced ototoxicity, and cisplatin-induced ototoxicity could not be explained by plasma Pt kinetics in individual animals.
Department of Speech Pathology and Audiology, School of Health and Rehabilitation Sciences, The University of Queensland, Brisbane, Australia.
Ravi
R
Sockalingam
Lucio
L
Filippich
Bruce
B
Charles
Bruce
B
Murdoch
D000158:Acoustic Impedance Tests; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001300:Audiometry, Evoked Response; D002945:Cisplatin / Q000633:toxicity*; D004285:Dogs; D005260:Female; D008297:Male; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects*; D010984:Platinum / Q000493:pharmacokinetics
D000970:Antineoplastic Agents; D010984:Platinum; D002945:Cisplatin