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新型铂类抗癌药物TRK-710与顺铂相比的耳毒性

Ototoxicity of the new platinum anticancer agent TRK-710 in comparison with cisplatin.

作者信息

Saito T, Manabe Y, Saito H

机构信息

Department of Otolaryngology, Fukui Medical School, Japan.

出版信息

ORL J Otorhinolaryngol Relat Spec. 1995 Sep-Oct;57(5):250-5. doi: 10.1159/000276752.

Abstract

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.

摘要

将新型铂类类似物TRK - 710(3、9、15mg/kg,连续3天)和顺铂(1、3、5mg/kg,连续3天)的药代动力学及耳毒性进行了比较。给药后1小时,TRK - 710的外淋巴浓度甚至仅为顺铂的七分之一。两组复合动作电位的N1阈值均呈剂量依赖性升高且听力损伤程度相似。利用相差显微镜和扫描电子显微镜进行的形态学观察显示,外毛细胞损伤程度基本相同,主要集中在基底转和第二转。尽管TRK - 710对顺铂耐药肿瘤有效,且肾毒性和骨髓抑制程度较轻,但临床使用时仍应与顺铂一样谨慎。

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