臓器内濃度および排出能よりみたカナマイシン難聴の発現機序

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Kanamycin(KM) levels in perilymph, blood, kidney, liver and brain were measured in KM pretreated(400 mg/kg, i.m.for 10 successive days) and untreated guinea pigs following an in-tramuscular injection of KM(400 mg/kg). In untreated group, KM levels in perilymph reached their peaks at 3 to 6 hr.after the in-jection, whereas those in other organs appeared within 1 hr.The maximum KM level observed in perilymph was quite high and preceded those in brain and blood.Similar patterns of the KM distribution was observed in the KM pretreated group except retention of considerably high KM levels even 24 hr.after the injection. The KM levels in kidney were higher than those in other organs and the elimination was slow.This tendency became more evident in KM pretreated groups where no appreciable eli-mination was seen even 24 hr.after the injection. The high level and slow elimination seems responsible for oto- and nephrotoxicities of KM. The toxicity of KM, however, may not be simply explained by differences in the level and eli-mination rate of KM, since in KM pretreated animals the liver has no noticeable damage inspite of maintaining s high level of KM. The content of acidic glycosaminoglycans(AGAG) in the lateral wall of cochlea, kidney and brain was analyzed electrophoretically.A considerably large quantity of AGAG was found in the lateral wall and it was found to be decreased significantly by KM treatments.It is known that elimination of KM from the inner ear is at least in part through the lateral wall of the cochlear duct.Since AGAG acts presumably as anions to bind KM having cationic pro-perties and possibly play an important role for eliminating them.Observed decrease in AGAG content of the lateral wall of cochlear duct may be a cause of the ototoxicity of KM by re-tarding the elimination of this drug from the perilymph.
社団法人日本耳鼻咽喉科学会の論文

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橘正芳
京都府立医科大学耳鼻咽喉科学教室

臓器内濃度および排出能よりみたカナマイシン難聴の発現機序

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