AGE-DEPENDENT CHANGE IN WARFARIN DISTRIBUTION VOLUME IN RATS : EFFECT OF CHANGE IN EXTRACELLULAR WATER VOLUME

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The pharmacokinetics of inulin was studied following intravenous administration of ^<14>C-inulin to 1-d, 1-, 3- and 8-week-old rats. The distribution volume of inulin varied 2-fold, from 689 ml/kg in 1-d-old rats to 340 ml/kg in 8-week-old rats in the growth process of rats. This result was similar to that of warfarin and there was a statistically significant correlation between the distributino volume of warfarin and inulin (r=0.984,p<0.02). In the growth process of rats, the K_P values of warfarin in muscle, which play an important role in the distribution kinetics of warfarin changed in parallel with those of inulin. These results and pharmacokinetic considerations indicated that in warfarin, which is highly bound to serum protein and shows a small distribution volume, the change in the distribution volume in the growth process of rats following administration of a pharmacologically realistic dose (1 mg/kg) is led by the change in the extracellular volume of tissues and that the change in serum protein binding of warfarin might play a minor role in the change in the distribution volume in the growth process.
公益社団法人日本薬学会の論文