Henley C M, Weatherly R A, Ou C N, Brown R D
Bobby R. Alford Department of Otorhinolaryngology and Communicative Sciences, Baylor College of Medicine, Houston, TX 77030, USA.
Hear Res. 1996 Sep 15;99(1-2):85-90. doi: 10.1016/s0378-5955(96)00094-9.
The developing rat is hypersensitive to aminoglycoside ototoxicity during the period of anatomical and functional development of the cochlea. Toxicity is expressed only after a few days of treatment when kanamycin is given during the most sensitive period for production of ototoxicity (postnatal days 11-20). In contrast, when the drug is administered after the 20th postnatal day, the same dose and duration of treatment do not produce an ototoxic effect. Only after prolonged treatment (e.g., > or = 20 days) is there an observed effect. We characterized the pharmacokinetics of kanamycin in the serum of 12- and 25-day-old rats and observed a greater than 2.5-fold increase in elimination half-life in the 12- versus 25-day-old rat. The longer duration half-life of kanamycin in younger rats may explain the hypersensitivity of immature mammals to aminoglycoside ototoxicity.
在耳蜗进行解剖和功能发育的时期，发育中的大鼠对氨基糖苷类耳毒性高度敏感。当在耳毒性产生的最敏感时期（出生后第11 - 20天）给予卡那霉素时，仅在治疗几天后才会表现出毒性。相比之下，当在出生后第20天之后给药时，相同的剂量和治疗持续时间不会产生耳毒性作用。只有经过长时间治疗（例如，≥20天）才会观察到效果。我们对12日龄和25日龄大鼠血清中卡那霉素的药代动力学进行了表征，观察到12日龄大鼠与25日龄大鼠相比，消除半衰期增加了2.5倍以上。卡那霉素在幼龄大鼠中较长的半衰期可能解释了未成熟哺乳动物对氨基糖苷类耳毒性的超敏反应。
