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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Toxicity, uptake, and subcellular distribution in rat hepatocytes of roxithromycin, a new semisynthetic macrolide, and erythromycin base.

Rat hepatocytes were used to study the toxicity of a new semisynthetic macrolide, roxithromycin, in comparison with erythromycin base and erythromycin estolate. Roxithromycin caused lactate dehydrogenase leakage close to that of erythromycin estolate and higher than erythromycin base after 21 h of exposure to the drugs. This effect was, at least in part, explained by the higher uptake: roxithromycin was two to three times more concentrated by liver cells than erythromycin base. For both roxithromycin and erythromycin base, the uptake depended on time, temperature, and extracellular antibiotic concentration. The accumulated macrolides egressed rapidly when cells were incubated in antibiotic-free medium. No uptake and no loss of accumulated drugs were observed at 4 degrees C. After accumulation by hepatocytes, roxithromycin and erythromycin base underwent similar subcellular distribution, mostly concentrating in cytosol and lysosomes. The small amount accumulated in the other particulate fractions followed the order mitochondria much greater than nuclei greater than microsomes. Roxithromycin, however, was less concentrated than erythromycin base in the microsomes.[1]

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