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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2004, Vol. 9 ›› Issue (3): 329-332.

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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   

  1. 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

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

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