Tissue distribution of 14C-midodrine and its active metabolite 14C-DMAE was investigated after oral and intravenous administration to rats using autoradiography and scintillation counting. Serum protein binding was also examined. After oral administration of 14C-midodrine at a dose of 3.4 pmol/kg, the radioactivity was distributed extensively throughout the body except for the central nervous system, testis and fat. High concentration of radioactivity was found in the gastrointestinal tract,

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... er and kidney followed by the lung, spleen, hypophysis and adrenal. The levels in these tissues were higher than that in the plasma. Elimination of radioacti vity from tissues paralleled that of plasma, and no marked accumulation in any tissue was found. Although the tissue concentrations in early time after oral admini stration of 14C-midodrine were higher than that in the case of '4C-DMAE, the distribution profiles were essentially similar in each case. However, 5 min after intravenous administration of 14C-midodrine or 14C-DMAE, the distribution profiles were found to be different from each other. DMAE and other metabolites were found in the tissues after the administration of 14C-midodrine and only a small amount of unchanged drug was detected. Serum protein binding of 14C-midodrine or 14C-DMAE in vitro was 10-20 % in rats , rabbits and dogs, and 24-31 % in human. The extent of serum protein binding of radioactive substances was about 22 % at 0. 5 hr after oral administration of 14C-midodrine to rats and was increased with time .