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KMID : 0370219960400030311
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Yakhak Hoeji
1996 Volume.40 No. 3 p.311 ~ p.319
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Compositional Change of Hepatic Bile Acid by Multiple Administration of DWP305, a Combined Preparation Containing Urosodeoxycholic Acid and Silymarin, in Rats
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조재열/Cho JY
연제덕/남권호/김점용/유은숙/유영효/박명환/Yeon JD/Nam KH/Kim JY/Yoo ES/Yu YH/Park MH
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Abstract
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DWP305, a preparation containing combination of ursodeoxycholic acid(UDCA), silymarin and vitamins (B1 and B2), is a drug currently being developed for hepatic disorders. In order to evaluate the changes in hepatic function by multiple oral administration(2 and 4 weeks) of DWP305 in rats, several biochemical parameters in blood, bile acid composition, and the accumulation of UDCA and lithocholic acid(LCA),a toxic metabolite formed by enterobacteria, were examined using HPLC. In blood biochemical findings, DWP305 did not affect the normal level and there was no difference in total bile acid composition for UDCA, cholic acid(CA), deoxycholic acid(DCA), chenodeoxycholic acid(CDCA) and LCA compared to the UDCA administered group, although total ratio of UDCA and CA was different from normal group. In case of ratio of taurine and glycine conjugated forms, DWP305(186mg/kg as a UDCA) administered group was also similar to normal group and UDCA administered group, while high dosing of DWP305 was not different in the ratio of UDCA administered group(930mg/kg) but normal group. And the ratio of LCA was in order of UDCA(930mg/kg), DWP305(930mg/kg as a UDCA), UDCA(186mg/kg) and DWP305(186mg/kg as a UDCA) administered group, which was less than 4%. The free form of UDCA as well as most of bile acids was not detected at all in rat liver, indicating that there’’s no accumulation. These results suggest that multiple dosing of DWP305 in rats may not affect hepatic biotransformation and metabolism of bile acids.
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