Quantitative indicators of gentamicin and sisomicin interaction with isolated subcellular fractions of the liver and kidneys and intracellular distribution of these antibiotics

: Interaction of gentamicin and sisomicin with isolated subcellular fractions of the rat liver and the kidney cortical layer was studied. Distribution of the antibiotics was investigated in a system with the volume ratio of the main components (organoids and cytosol-dissolved drug) simulating the natural volume ratio of the cytoplasm and organoids in the cells. It was shown that lysosomes were the most active elements in binding antibiotics. The microsomes and mitochondria were less active. By the binding capacity the subcellular structures of the kidneys were superior to the analogous structures of the liver. Dissociation of the organoid complexes with the antibiotics was possible, the mobility of the sisomicin complexes being higher than that of the gentamicin complexes. During intracellular distribution the major amount of every of the above aminoglycosides was absorbed by the organoids. Up to 20 per cent of gentamicin and up to 30 per cent of sisomicin remained in the cytoplasm in the active form. The characteristic features of the intracellular distribution of sisomicin (build up of high levels of the free antibiotic in the cytoplasm and relatively easy dissociation of the antibiotic complexes with the organoids of the kidney cortical layer) may define the higher activity of sisomicin as compared to that of gentamicin against intracellularly located microorganisms and its lower potential nephrotoxicity.