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Acta Otolaryngol (Stockh) 1988 May-Jun;105(5-6):511-5

Aminoglycoside ototoxicity: influence of dosage regimen on drug uptake and correlation between membrane binding and some clinical features.

Tran Ba Huy P, Deffrennes D

Departement de Physiologie, Faculte Xavier Bichat, Universite Paris 7, France.

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.

PMID: 3261106, UI: 88291804

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