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.
Sockalingam
Ravi
R
Department of Speech Pathology and Audiology, School of Health and Rehabilitation Sciences, The University of Queensland, Brisbane, Australia.
Filippich
Lucio
L
Charles
Bruce
B
Murdoch
Bruce
B
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