Uptake of Pyrithiamine by Tissues of Rats in Relation to Tissue Thiamine Levels

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  • 森田 実
    Shionogi Research Laboratory, Shionogi and Co., Ltd.
  • 金谷 尚
    Shionogi Research Laboratory, Shionogi and Co., Ltd.
  • 峰下 銕雄
    Shionogi Research Laboratory, Shionogi and Co., Ltd.

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Uptake of pyrithiamine (PyT) by tissues of normal and thiamine-deficient rats was compared.<br>1. PyT concentration in livers of both normal and thiamine deficient rats reached a maximal level of approximately 20μg/g within 1 hour after the intraperitoneal injection of 10mg/kg of PyT, and then decreased. The rate of decrease of PyT was much slower in the deficient liver than in the normal one. The former retained about 8μg/g of PyT even after 6 days, while the latter retained less than 0.5μg/g.<br>2. Brain and muscular tissues took up PyT very slowly, and the maximal concentrations were obtained 24 to 48 hr after the injection. PyT levels in these tissues of the deficient rats were markedly higher and maintained for a longer time than that of normal ones.<br>3. The thiamine levels in tissues of PyT treated normal rats decreased temporarily in accordance with the time of PyT accumulation. In thiamine-deficient tissues except brain, thiamine levels decreased to a very low level and were not further affected by PyT administration. The brain thiamine level decreased by the injection of PyT.<br>4. The increased PyT levels of PyT treated thiamine-deficient rats were quickly decreased by the administration of thiamine.<br>5. Most of the PyT taken up by the tissues of thiamine-deficient rats was present as the phosphorylated form.<br>6. When an equimolar amount of PyT or thiamine was administered to thiamine-deficient rats, more PyT was taken up by the tissues than thiamine. Coadministration of PyT and thiamine caused reduction of the uptake of both compounds.<br>7. The mechanism of the thiamine lowering action of PyT was discussed.

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