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  • Title: [Sisomicin pharmacokinetics in rat tissues in single and long-term administration].
    Author: Umnova LV, Koroleva VG, Goncharskaia TIa, Firsov AA, Fomina IP.
    Journal: Antibiotiki; 1981 Aug; 26(8):612-7. PubMed ID: 7294752.
    Abstract:
    The pharmacokinetics of sisomicin administered intramuscularly to rats in daily doses of 12.5 and 25 mg/kg for 30 days was studied. After a single administration of the drug in the above doses the highest and the lowest levels of sisomicin were observed in the kidney cortical layer and liver, respectively. The antibiotic level in the tissues rose with an increase in the antibiotic dose and duration of the drug use. The two-fold rise in the dose resulted in an elevation in the sisomicin level in the kidney cortical layer by 1.7 times, in the medullary layer by 3 times, and in the blood serum, lungs and spleen by 2.3, 1.2 and 1.5 times, respectively. After treatment with a dose of 25 mg/kg for 8 days the antibiotic level in all tissues studied was higher than that after the first administration of the drug: in the cortical and medullary layers of the kidneys by 5-7 times and in the blood serum and other tissues by 1.2-2 times. When sisomicin was used repeatedly in any dose, stabilization of or some decrease in the mean integral concentration of the antibiotic in the kidney cortical layer and a continuous increase of this value with respect to the medullary layer (up to the 30th day) were noted. The difference between the antibiotic levels in the kidney layers after the repeated administration of the drug was less pronounced than that after a single administration of the drug. The cumulation index of sisomicin in the kidney cortical layer persisted at the same level and that in the medullary layer gradually increased. In this connection it is concluded that correlation between the sisomicin nephrotoxic effect and the level of the antibiotic in the kidney cortical layer is more pronounced than that in the medullary layer.
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