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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.
C M Henley, and
R A Weatherly, and
C N Ou, and
R D Brown
January 1994,
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery,
C M Henley, and
R A Weatherly, and
C N Ou, and
R D Brown
February 1976,
Veterinariia,
C M Henley, and
R A Weatherly, and
C N Ou, and
R D Brown
February 1984,
Teratology,
C M Henley, and
R A Weatherly, and
C N Ou, and
R D Brown
January 1987,
Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology,
C M Henley, and
R A Weatherly, and
C N Ou, and
R D Brown
June 1974,
Clinical pharmacology and therapeutics,
C M Henley, and
R A Weatherly, and
C N Ou, and
R D Brown
January 1992,
Veterinary research communications,
C M Henley, and
R A Weatherly, and
C N Ou, and
R D Brown
March 1981,
Antibiotiki,
C M Henley, and
R A Weatherly, and
C N Ou, and
R D Brown
July 1976,
Antibiotiki,
C M Henley, and
R A Weatherly, and
C N Ou, and
R D Brown
December 1974,
Antimicrobial agents and chemotherapy,
C M Henley, and
R A Weatherly, and
C N Ou, and
R D Brown
April 1992,
Antibiotiki i khimioterapiia = Antibiotics and chemoterapy [sic],
