Pharmacokinetics of gentamicin in the sensory hair cells of the organ of Corti: rapid uptake and long term persistence.
Confocal laser scanning microscopy and immunofluorescence were used to detect gentamicin at the single cell level in the sensory cells of the guinea-pig hearing organ after a chronic systemic treatment. Gentamicin uptake by the hair cells precedes largely the manifestation of hearing impairment. We demonstrate that for a non-ototoxic treatment the captured gentamicin is eliminated in two phases: one rapid and one slow with approximate half-life of 2 days and 5-6 months, respectively. These novel observations should be of primary importance for new rational approaches to both the mechanism of ototoxicity and therapeutic strategies for the treatment of infectious diseases requiring the aminoglycoside antibiotics.
Dulon
D
D
Laboratoire d'Audiologie, Expérimentale, INSERM U 229, Université de Bordeaux-II, Hôpital Pellegrin, France.
Hiel
H
H
Aurousseau
C
C
Erre
J P
JP
Aran
J M
JM
D000818:Animals; D005260:Female; D005455:Fluorescent Antibody Technique; D005839:Gentamicins / Q000493:pharmacokinetics*; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000378:metabolism*; D066298:In Vitro Techniques; D007834:Lasers; D008855:Microscopy, Electron, Scanning / Q000379:methods; D009925:Organ of Corti / Q000166:cytology*
D005839:Gentamicins