Comparative studies for disposition of (14C)hydralazine, (14C)budralazine and (14C)cadralazine in rats.

Abstract

For elucidation of common characteristics in disposition of hydralazine vasodilators, distribution of [14C]hydralazine and [14C]budralazine was studied in normal rats at the time points of their maximal tissue levels and at 24 hr after single and 10 consecutive daily oral administration and was compared with that of [14C]cadralazine. Doses were set to be virtually equipotent to each other from the aspect of their maximal antihypertensive activity. For comparison, following three parameters were used: tissue/plasma concentration ratios, the ratio of concentrations observed 24 hours after administration to maximal tissue concetration and tissue levels after repeated/single administration. 1. The distribution of the agents was commonly significat in liver and kidney being conceivably related with their disposition, and was rather selective to the possible target vasculature, aorta as a representative. The rate of disappearance of radioactivity seemed to be slower in common tissues: e.g., in erythrocytes, aorta, brain, lung, Harderian gland, thyroid and adipose tissue. 2. After repeated administration, the change in distribution pattern relative to that after single administration was significant in the following order of [14C]budralazine (increase of tissue concentration in aorta, erythrocytes, spleen and skin)> cadralazine (in erythrocytes)≥hydralazine (in adipose tissue). The rate of disappearance was slower in such commonn tissues which are rich in collagen content (e.g., aorta, skin, lung, trachea etc). Accumulation of radioactivity was significant in 12 tissues for [14C]cadralazine, 13 tissues for [14C]hydralazine and 21 tissues for [14C]budralazine.