• The Korean Journal of Pharmacology
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• v.9 no.1
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• pp.39-46
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• 1973

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.

• Journal of Society of Preventive Korean Medicine
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• v.17 no.2
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• pp.139-155
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• 2013

Purpose : This study was aim to evaluate effects of pharmacodynamics and toxicity in combination therapy of donepezil with Gongjindan. The effects of Gongjindan co-administration on the pharmacokinetics (PK) of donepezil were observed after single and 7-day repeated oral co-administration with 1.5hr-intervals, to evaluate synergic pharmacodynamics and reduce toxicity of combination therapy of donepezil with Gongjindan. Materials and Methods : After 10mg/kg of donepezil treatment, Gongjindan100mg/kg was administered with 1.5hr-intervals. The plasma were collected at 30min before administration, 30min, 1, 2, 3, 4, 6, 8 and 24hrs after end of first and last 7th donepezil treatment, and plasma concentrations of donepezil were analyzed using LC-MS/MS methods. Results : Gongjindan markedly inhibited the absorption of donepezilregardless of sample time, from 30min to 8hrs after end of first 1.5hr-interval co-administration as compared with donepezil single treated rats. Especially the absorption of donepezil was significantly decreased at 2, 4, 6 and 8hrs after co-administration as compared with donepezilsingle treated rats. Accordingly, the Cmax (-26.236%), $AUC_{0-t}$(-26.02%) and $AUC_{0-inf}$(-25.90%) of donepezil in 1.5hr-interval co-administered rats were dramatically decreased as compared with donepezilsingle treated rats, respectively. However, no meaningful changes on the plasma donepezil concentrations and pharmacokinetic parameters were detected after end of last 7th 1.5hr-interval co-administration as compared with donerezil single treated rats, except for non-significant slight increases of Tmax(16.67%) detected in co-administered rats as compared with donepezil single treated rats. Conclusion : These findings are considered as direct evidences that Gongjindan also decreased oral bioavailability of donerezil as inhibited the absorptions, when they were co-administered with 1.5hr-intervals, but they may be adapted after 7 days continuous repeated l.5hr-interval co-administration.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2008.04a
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• pp.5-20
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• 2008

GLP-1-based drugs (GLP-1 analogues and DPP IV inhibitors) and incretin mimetics are currently one of the most exciting classes of agents for type II diabetes. GLP-1, a gut peptide, is an incretin that potentiates glucose-dependent insulin release from the pancreas, slows GI-transit and stimulates the proliferation of beta-cells. DPP IV inhibitors act like incretins by inhibiting DPP IV which inactivates GLP-1. LC15-0133 is a competitive, reversible DPP IV inhibitor ($IC_{50}$ = 24 nM, Ki=0.247 nM) with excellent selectivity over other critical human proteases such as DPP II, DPP 8, elastase, trypsin. and urokinase. LC15-0133 showed long half-life and good bioavailability in rats and dogs. Inhibition of plasma DPP IV activity by LC15-0133 was kept more than 50% 24 hours after oral dosing in rats and dogs at 0.1 mg/kg and 0.02 mg/kg, respectively. The Minimum effective doses of LC15-0133 were 0.01 mg/kg for lowering blood glucose excursion during oral glucose tolerance test and 0.1 mg/kg for increasing glucose-induced GLP-1 response in C57BL/6 mice. Repeat oral administration of LC15-0133 for 1 month delayed the progression to diabetes and reduced HbA1c levels in a dose-dependent manner in Zucker Diabetic Fatty rats. In conclusion, LC15-0133 is a novel, potent, selective and orally active DPP IV inhibitor and showed an excellent blood glucose lowering effects in various animal models.