庆大霉素对不同年龄组豚鼠的药动学与耳毒性研究

中国临床药理学与治疗学 ›› 2004, Vol. 9 ›› Issue (3): 329-332.

庆大霉素对不同年龄组豚鼠的药动学与耳毒性研究

朱新波, 王菊香¹, 董缪武, 王珊娟, 林丹, 金晓冬

温州医学院药理教研室, 温州325027, 浙江;
¹温州医学院附属育英儿童医院, 温州325000, 浙江

收稿日期:2003-10-24 修回日期:2003-12-10 出版日期:2004-03-26 发布日期:2020-11-21
通讯作者: 朱新波, 男, 讲师, 研究方向:临床药理、神经药理。Tel:0577-88833462 　E-mail:wzzhuxinbo@sina.com
基金资助:
浙江省温州市科技局基金资助项目(№01025)

Experimental study on ototoxicity of gentamycin at therapeutic doses in infant or adult guinea pigs

ZHU Xin-Bo, WANG Ju-Xing¹, DONG Miao-Wu, WANG Shan-Juan, FANG Zhou-Xi, LIN Dan, JING Xiao-Dong

Department of Pharmacology, Wenzhou Medical College, Wenzhou 325027, Zhejiang, China;
¹Department of emergency, the Second Teaching Hospital of Wenzhou Medical College, Wenzhou 325000, Zhejiang, China

Received:2003-10-24 Revised:2003-12-10 Online:2004-03-26 Published:2020-11-21

摘要/Abstract

摘要： 目的:观察庆大霉素治疗剂量对幼年和成年豚鼠耳毒性的程度有无差异。方法:幼年组、成年组豚鼠各35 只, 对照组各7 只。按照与人类等效剂量肌肉注射庆大霉素, 用高效液相法分析两组药动学特点;用光镜和电镜观察两组耳蜗损伤情况。结果:单剂给药2 组均为二室开放模型, 峰浓度和达峰时间差异无显著性;多次给药幼年组血药浓度明显高于同点成年组, 存在明显体内药物蓄积;耳蜗损伤情况, 幼年组较成年组重, 且停药后毛细胞缺失数持续增加。结论:等效人类治疗剂量的庆大霉素对幼年组豚鼠造成的耳毒性损害较成年组严重, 且随用药时间延长而加重。幼年豚鼠的这种高敏性可能与药物从体内排出慢、易蓄积有关。

关键词: 庆大霉素, 药动学, 耳毒性, 豚鼠

Abstract: AIM: To clarify the differences of ototoxicity and pharmacokinetics of gentamycin between infant and adult guinea pigs with therapeutic doses equal to clinical doses and its causes.METHODS: There were 35 guinea pigs in each infant or adult group.Seven guinea pigs in each group were used as control.Gentamycin was intramuscularly injected at a dose of 15 000 U·kg ^-1 (adult) or 20 000 U·kg ^-1 (infant) once a day for 14 days, which was equal to the clinical therapeutic dose.7 guinea pigs in each group were sacrificed for histological and scanning electron-microscopic examination of cochlea on the day after 5, 7, 10 and 14 days of drug administration, as well as on 28th day.Pharmacokinetic parameters were investigated in all by HPLC.RESULTS: The pharmacokinetic parameters were compatible with the model of two compartments in all age groups.There were no significant difference in the peak level and peak time between the groups.The blood levels of gentamycin after daily administration in infant guinea pigs were predominantly higher than those in adult groups, and were increased markedly since 14th day.These results indicated that there was an increased accumulation of gentamycin in in-fant guinea pigs.In histological examination of cochlea, many stereocilia were found lie down or disappear and a number of outer hair cells were found disappeared on 7th day in infant group on scanning electron-microscopy while on 10th day in adult group.Microscopic observation showed that more hair cells were absent in neonatal group than in infant and adult groups after 10th day.The hair cell absence was more obvious in infant group than in adult group.The severity of cochlea damage became worse with a prolonged course of gentamycin administration.Continuous damage was observed within 2 weeks after the drug administration in two groups.CONCLUSION: A close attention should be paid to the danger of ototoxocity caused by aminoglycosides in children even they are administrated at a dose recommended by pharmacopeia and for a regular course.

Key words: gentamycin, pharmacokinetics, ototoxicity, guinea pig

中图分类号:

朱新波, 王菊香, 董缪武, 王珊娟, 林丹, 金晓冬. 庆大霉素对不同年龄组豚鼠的药动学与耳毒性研究[J]. 中国临床药理学与治疗学, 2004, 9(3): 329-332.

ZHU Xin-Bo, WANG Ju-Xing¹, DONG Miao-Wu, WANG Shan-Juan, FANG Zhou-Xi, LIN Dan, JING Xiao-Dong. Experimental study on ototoxicity of gentamycin at therapeutic doses in infant or adult guinea pigs[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(3): 329-332.

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