The Tissue-Disposition of Gentamicin in Rats

Abstract: The tissue disposition of ¹⁴C-gentamicin was studied in young rats after a single-dose administration by autoradiographic techniques. The autoradiograms showed a high accumulation of the substance in non-parenchymateous tissues such as cartilages and connective tissues and a strong uptake in the kidney cortex. The in vivo bound substance was displaced from the cartilage at incubations in cation-containing solutions, indicating an ionic binding of the polycationic gentamicin to negatively charged groups in the cartilage (probably carboxyl and sulphate groups of chondroitin sulphate). In the inner ear a localization of the substance was found in the membraneous walls of the chochlea and, at short survival intervals, in the perilymph, whereas the radioactivity in the endolymph was low. Studies in vitro showed an ionic binding of gentamicin to cartilage and in addition to several other tissues, such as the lymphomyeloid system, the gastrointestinal mucosa, the exocrine pancreas, salivary glands, and most prominent, the pigmented tissues. A strong in vitro binding of gentamicin to pigment from beef eyes was also shown. The potential binding sites in the latter tissues are localized intracellularly and are therefore apparently unattainable for the charged hydrophilic gentamicin molecule in vivo.