title: Pharmacokinetics of kanamycin in the developing rat.
abstract: 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.
authors.affiliation: Bobby R. Alford Department of Otorhinolaryngology and Communicative Sciences, Baylor College of Medicine, Houston, TX 77030, USA. chenley@bcm.tmc.edu
authors.forename: C M
authors.initials: CM
authors.lastname: Henley
authors.forename: R A
authors.initials: RA
authors.lastname: Weatherly
authors.forename: C N
authors.initials: CN
authors.lastname: Ou
authors.forename: R D
authors.initials: RD
authors.lastname: Brown
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D003051:Cochlea / Q000187:drug effects* / Q000502:physiology; D006207:Half-Life; D007273:Injections, Intramuscular; D007612:Kanamycin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D008297:Male; D051381:Rats
chemical_list: D000900:Anti-Bacterial Agents; D007612:Kanamycin