title: Aminoglycoside ototoxicity: influence of dosage regimen on drug uptake and correlation between membrane binding and some clinical features.
abstract: The influence of dosage regimen on gentamicin uptake by the inner ear tissues was investigated by radioimmunoassay in rat given single i.m. 10 or 100 mg/kg injection or i.v. 1.5 or 15 micrograms/min constant infusion. Results show that, for a given dose, discontinuous administration yields markedly lower tissue concentration than continuous administration and, thus, carries less ototoxic risk. Using 125I-labelled gentamicin as a radioligand correlation between membrane binding and clinical features was also studied in homogenates of organ of Corti and vestibular maculae of guinea-pig. Results show that: (i) as compared by Kd values, gentamicin exhibits a four-fold greater affinity for vestibule (Kd = 3 X 10(-7) M) than for cochlea (Kd = 1.2 X 10(-6) M). This explains the predilection of this antibiotic to affect the vestibular apparatus; (ii) the typical baso-lateral progression of ototoxic degeneration cannot be accounted for by a preferential uptake of the drug between base and apex.
authors.affiliation: Departement de Physiologie, Faculté Xavier Bichat, Université Paris 7, France.
authors.forename: P
authors.initials: P
authors.lastname: Tran Ba Huy
authors.forename: D
authors.initials: D
authors.lastname: Deffrennes
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000633:toxicity*; D001665:Binding Sites; D003051:Cochlea / Q000187:drug effects; D007758:Ear, Inner / Q000187:drug effects*; D005839:Gentamicins / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D014722:Vestibule, Labyrinth / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins