Age-dependent changes in warfarin tissue distribution.

Whole blood levels, serum protein binding and tissue concentration following intravenous administration of warfarin were investigated in 1-d-old, 1-, 3- and 8-week-old rats to determine the drug disposition in the growth process. It was shown that the clearance of warfarin in 1-d-old or 1-week-old rats was considerably lower than that in 3- or 8-week-old rats. The decrease in clearance in infant and young rats was considered to be caused by the immaturity of the physiological function of the liver to remove exogenous compounds. The distribution volume in 1-d-old or 1-week-old rats was larger than that in 3- or 8-old rats. The percentages of serum free warfarin in 1-d-old and 1-week-old rats were about twice those in 3- and 8-week-old rats. The increased distribution volume in infant rats was considered to be caused by a lower serum protein binding in these rats.