Pharmacokinetics of aminoglycoside antibiotics in blood, inner-ear fluids and tissues and their relationship to ototoxicity.
This review critically evaluates the literature on aminoglycoside pharmacokinetics in order to answer the question how fluid and tissue levels of the drugs relate to the development of ototoxic and nephrotoxic side effects. We will summarize the evidence that: (1) aminoglycosides do not accumulate in inner-ear fluids; (2) aminoglycoside levels in fluids do not correlate with the ototoxic potential of a drug, and (3) selective toxicity cannot be explained by selective tissue penetration of the drugs. We suggest that studies of drug disposition at the cellular level after chronic aminoglycoside treatment be conducted to establish whether a cell-specific uptake contributes to the selective toxicity of the aminoglycoside antibiotics. A sequence of biochemical events that may lead to the development of toxicity at the molecular level is briefly described.
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000633:toxicity; D004427:Ear Diseases / Q000139:chemically induced*; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced; D007761:Labyrinthine Fluids / Q000378:metabolism*; D014018:Tissue Distribution
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents