DISPOSITION OF SALICYLIC ACID IN ANALBUMINEMIC RATS

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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 ¹⁴C-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.