Ototoxicity of the new platinum anticancer agent TRK-710 in comparison with cisplatin.
The pharmacokinetics and ototoxicity of the new platinum analogue TRK-710 (3, 9, 15 mg/kg x 3 days) were compared with those of cisplatin (1, 3, 5 mg/kg x 3). The perilymphatic concentration of TRK-710 was one seventh of that of cisplatin even 1 h after the administration. The N1 threshold of the compound action potential was elevated dose-dependently in both groups with a similar degree of hearing impairment. Morphological observation using phase contrast microscopy and scanning electron microscopy revealed the damage of the outer hair cells to almost the same degree mainly in the basal and second turns. Despite its usefulness against cisplatin-resistant tumors and a lesser degree of nephrotoxicity and myelosuppression, TRK-710 should be clinically used with caution similar to cisplatin.
Saito
T
T
Department of Otolaryngology, Fukui Medical School, Japan.
Manabe
Y
Y
Saito
H
H
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D001300:Audiometry, Evoked Response; D001309:Auditory Threshold / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D003051:Cochlea / Q000187:drug effects* / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000648:ultrastructure; D006309:Hearing / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008855:Microscopy, Electron, Scanning; D008858:Microscopy, Phase-Contrast; D009925:Organ of Corti / Q000187:drug effects / Q000648:ultrastructure; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D010498:Perilymph / Q000737:chemistry
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C098268:TRK 710; D002945:Cisplatin