Studies on Absorption Distribution and Excretion of 2-2-Methylene bis (3, 4, 6-trichlorophenoxy acetic acid) (MTPA) in Rabbits

2-2-Methylene bis (3, 4, 6-trichlorophenoxy acetic acid) (MTPA)의 체내흡수(體內吸收) 분포(分布) 및 배설(排泄)에 관(關)한 연구(硏究)

It has been reported previously that 2,2-methylene bis(3,4,6-trichlorophenoxy acetic acid) (MTPA) is effective treating for clonorchiasis and less toxic to the hosts. In this studies the absorption, distribution and excretion of MTPA were observed. For this purpose $^{14}C-MTPA$ was synthesised from bis(2-hydroxy-3,5,6-trichlorophenoxyl) methan $^{14}C$ and administerd to the normal rabbit in a single dose of 10mg/kg IV or 20 mg/kg P.O. or to the Clonorchis infected rabbit in dose of 20 mg/kg/day for 6 days. Radioactivity in blood, tissue, bile, urine, feces and tissue of the fluke was measured after the drug was given. The concentration of MTPA in these samples were calcurated from the radioactivity. The result obtained as followes. 1. The increase in concentration of MTPA in blood and urine after oral administration of MTPA was so slow that the absorption of MTPA from the gastrointestinal tract appears very slow. 2. It is presumed that the excretion of MTPA also is slow because the reduction of MTPA concentration in blood after IV injection was very slow. 3. Large amount of MTPA was excreted from the bile. 4. During repeat dose of 20mg/kg/day for 6 days the concentration of MTPA in blood and tissue gradually increased. 5. The highest concentration of MTPA in the kidney and liver, heart, lung, spleen and muscle in decreasing order and the lowest concentration in the brain was noted. 6. During daily dose of 20 mg/kg of MTPA for 6 days of administration the concentration of MTPA gradually increased in urine and feces and the concentration of MTPA in feces was higher than of in urine. It appeares that MTPA take place enterophepatic circulation. 7. It is assumed that accumulation in large amount of MTPA in the liver and tissue of clonorchis, excretion of large amount from the bile is a favorable property of MTPA as a chemotherapeutic agent for clonorchiasis.