Objective:To clarify the possibility of higher sensitivity to ototoxicity of aminoglycosides in neonatal animal.Methods:The difference in ototoxicity was studied by scanning electron-microscopy and microscopy between neonatal and adult groups of 36 guinea pigs administrated with therapeutic doses of amikacin.Pharmacokinetics was investigated in 10 guinea pigs in each group by TDx system.Results:(1)The pharmacokinetics were compatible with the model of two compartment in all age groups.There was no significant difference in the peak level and peak time.Compared with adult group

the plasma clearance was lower(0.0044±0.0011 and 0.0088±0.0014 L/min. kg

P <0.01)

the half-life for elimination longer in neonatal group(70.89±13.38和43.24±8.03min

P <0.01)

and AUC was larger(11461.5±4317.2和8165.9±3212.5

P <0.01).(2)On histological study for cochlea

the damage was more severe in neonatal groups than that in adults.The severity of cochlea damage was getting worse with a prolonged course of the administration.Continuous damage was observed after the drug had been stopped.Conclusion:The study shows that there is significant ototoxicity of AMK to cochlea in neonatal guinea pigs even with therapeutic doses equal to that in clinical use.The higher sensitivity to ototoxicity of AMK in neonatal animal is related to their much slow clearance and high possibility of accumulation for AMK.