Disposition of salicylic acid in analbuminemic rats

  • HIRATE J.
    Department of Hospital Pharmacy, Toyama Medical and Pharmaceutical University
  • HORIKOSHI ISAMU
    Department of Hospital Pharmacy, Toyama Medical and Pharmaceutical University
  • WATANABE JUN
    Department of Biopharmaceuics, Faculty of Pharmaceutical Sciences, Nagoya City University
  • OZEKI SHOJI
    Department of Biopharmaceuics, Faculty of Pharmaceutical Sciences, Nagoya City University
  • NAGASE SUMI
    Department of Chemistry, Sasaki Institute

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To clarify the role of albumin in the dispositions of drugs by in vivo experiment, analbuminemic rats were used and plasma-level analyses and whole-body autoradiography following intravenous administration of ^<14>C-salicylic acid were carried out. The distribution volume of salicylic acid in analbuminemic rats (650±33 ml/kg) was remarkably larger than that in normal rats (180±3 ml/kg) (p <0.01). Whole-body autoradiograms demonstrated that transfer of salicylic acid from the blood to the liver, muscle and brain, especially to the liver, may be increased in analbuminemic rats. The increased distribution may be explained by the lack of plasma albumin, since the distribution of salicylic acid depends in part on plasma albumin binding. The total body clearance of salicylic acid in analbuminemic rats (12.2±1.4 ml/min/kg) was about 3.2 times that in normal rats (3.8±0.1ml/min/kg) (p <0.01), suggesting that metabolic clearance and/or renal clearance is enhanced in analbuminemic rats. Increased extraction by the liver and/or the kidney due to increased free fraction in total (bound and unbound) plasma salicylic acid assumed to be responsible for this result.

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  • J. Pharmacobio-Dyn.

    J. Pharmacobio-Dyn. 7 (12), 929-934, 1984

    公益社団法人日本薬学会

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