Endolymph aminoglycosides

This difference in half-lives in serum and tissues was misinterpreted in the early literature as an accumulation of aminoglycosides in the inner ear and held responsible for their organ-specificity. Such an interpretation is, however, not tenable. Aminoglycoside antibiotics are present in the fluids (perilymph and endolymph) and the tissues of the inner ear at relatively low levels, typically at one-tenth of peak serum levels. The reason for the differential sensitivity of inner ear sensory cells may then be based on the extreme persistence of the drugs or on an intrinsic susceptibility to their actions, notably to the generation of reactive oxygen species as described later. ... 

Distribution All of the aminoglycosides have similar pharmacokinetic properties. Levels achieved in most tissues are low, and penetration into most body fluids is variable. Concentrations in cerebrospinal fluid are inadequate even when the meninges are inflamed. Except for neomycin, the aminoglycosides may be administered intrathecally. High concentrations accumulate in the renal cortex and in the endolymph and perilymph of the inner ear, which may account for their nephrotoxic and ototoxic potential. All cross the placental barrier and may accumulate in fetal plasma and amniotic fluid. 

Etacrynic acid potentiates aminoglycoside ototoxicity by facilitating the entry of the antibiotics from the systemic circulation into the endolymph (33). Animal evidence suggests that this effect may be potentiated by glutathione depletion (34). Conversely, neomycin can enhance the penetration of etacrynic acid into the inner ear (35). 

Li H, Steyger PS (2011) Systemic aminoglycosides are trafficked via endolymph into cochlear hair cells. Sci Rep 1 159... 

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