PHARMACOKINETICS OF KANAMYCIN IN THE DEVELOPING RAT

The developing rat is hypersensitive to aminoglycoside ototoxicity dur ing the period of anatomical and functional development of the cochlea . Toxicity is expressed only after a few days of treatment when kanamy cin is given during the most sensitive period for production of ototox icity (postnatal days 11-20). In contrast, when the drug is administer ed after the 20th postnatal day, the same dose and duration of treatme nt do not produce an ototoxic effect, Only after prolonged treatment ( e.g., greater than or equal to 20 days) is there an observed effect. W e 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 e limination half-life in the 12- versus 25-day-old rat. The longer dura tion half-life of kanamycin in younger rats may explain the hypersensi tivity of immature mammals to aminoglycoside ototoxicity.