INFLUENCE OF DEHYDRATION AND D-GLUCARATE ON DISTRIBUTION AND EXCRETION OF KANAMYCIN IN RATS

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Abstract
Effects of dehydration and sodium D-glucaro-1,4-lactone on kanamycin distribution in the kidneys, liver, lungs, spleen and cochleae were determined after i.m. injection of the antibiotic to male rats. Coincident changes in plasma concentration and urinary excretion were measured. After administration of 30 mg/kg, dehydrated rats showed slower plasma elimination and urinary excretion as compared with normal animals. When dehydrated rats were pretreated with sodium D-glycaro-1,4-lactone, the plasma half-life of drug elimination and rate of urinary drug excretion closely paralleled those of normal animals. In the organ distribution study, dehydrated rats showed delayed removal of kanamycin from all organs as compared with normal animals. The extremely high level of the antibiotic in the kidney was about 2 orders of magnitude higher than found in other organs. The kidney showed different time course patterns for tissue levels in dehydrated rats. In dehydrated rats given sodium D-glucaro-1,4-lactone, the antibiotic levels in all organs followed the same pattern as in normal rats. When a lower dose was given to the dehydrated rats, the drugs was cleared from the plasma with a decreased half-life. The tissue distribution percentages decreased in all organs as the dose was lowered in dehydrated rats and with 1 mg/kg of kanamycin, only the kidney content was higher than that in sodium D-glucaro-1,4-lactone-treated animals.

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