Absorption and excretion of
14C-labeled midodrine were compared with those of
14C-DMAE, which is active metabolite of midodrine, after oral administration of each compound at equimolar dose (3.4 μmol/kg) in rats and dogs. Absorption of
14C-midodrine in rats has been shown to occur mainly from the intestine, and was faster than that of
14C-DMAE. During the process of absorption, DMAE was formed extensively by cleavage of the glycine molecule of midodrine. After oral administration of
14C-midodrine, the peak blood level of radioactivity was attained at 0.5 hr in rats and 1.25 hr in dogs, and was followed by a biexponential decline. In dogs given
14C-midodrine orally, the peak plasma level of unchanged midodrine, accounted for 14 % of total radioactivity, and was attained 0.75 hr after dosing, thereafter declined with a half-life of 4.71 hr. The active metabolite DMAE appeared in the plasma over the same period and the levels exceeded those of unchanged midodrine 0.75 hr after administration. The AUC value of DMAE (AUC
DMAE) after administration of
14C-midodrine was apparently higher than that after
14C-DMAE dosing in dogs. In both species, urinary excretion was the predominant elimination route accounting for 89.0 % of the dose in rats and 97.4 % in dogs during 5 days after dosing. Biliary excretion accounted for 28.7 % of the dose in rats within 30 hr after oral dosing. In addition, enterohepatic circulation was demonstrated. Similar excretion profiles were observed in the case of
14C-DMAE.
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