Furosemide-induced alteration of drug pathway to cochlea.
The ototoxicity of aminoglycosides is known to be enhanced by post-treatment with loop diuretics. The present experimental study was undertaken to elucidate the mechanism of this enhancement immunohistologically. Intravenously administered kanamycin (KM) reached the organ of Corti rapidly (within 10 min) via the capillaries of the basilar membrane and spiral limbus. Besides this direct pathway, KM penetrated through the perilymphatic space pathway. This penetration, however, took a much longer time (90 min). In contrast, in the case when KM was followed by intravenous furosemide (FM), KM reached the perilymphatic region within a short time (1-5 min). The KM content of the organ of Corti ascertained 1-5 min after FM injection seemed almost equivalent to that determined 90 min after injection of KM alone. This FM-induced change in the time-course penetration pattern of KM might have a bearing on the enhancement of its otoxicity.
Yamane
H
H
Department of Otolaryngology, Osaka City University Medical School, Japan.
Nakai
Y
Y
Konishi
K
K
D000818:Animals; D003051:Cochlea / Q000187:drug effects*; D004357:Drug Synergism; D005455:Fluorescent Antibody Technique; D005665:Furosemide / Q000494:pharmacology*; D006168:Guinea Pigs; D007612:Kanamycin / Q000493:pharmacokinetics / Q000633:toxicity*; D009925:Organ of Corti / Q000187:drug effects; D013997:Time Factors
D007612:Kanamycin; D005665:Furosemide