摘要
Ursodeoxycholic acid (UDCA) has beneficial effects in cholestatic liver diseas es. Inprimary sclerosing cholangitis (PSC), there is evidence that high doses ( ±20 mg/kg) of UDCA may be more effective than average doses. Biliary enrichment of UDCA at such high doses may represent the decisive factor for its beneficial effect. Up to now it is not clear how highdose UDCA correlates with its biliary enrichment and whether bacterial degradation of large amounts of UDCA may lead to an increased bacterial formation of more toxic hydrophobic bile acids. We det ermined the biliary bile acid composition in 56 patients with PSC including 30 p atients with repeat bile samples treated with various doses of UDCA. At a UDCA d ose of 10-13 mg/kg/d (n = 18) biliary UDCA represented 43.1%+0.3%(mean +SD) of total bile acids; at a UDCA dose of 14-17 mg/kg (n = 14), its biliary conte nt increased to 46.9%+0.3%, at 18-21 mg/kg (n = 34) to 55.9%+0.2%, at 22 -25 mg/kg (n = 12) to 58.6%+2.3%, and at 26-32 mg/kg (n = 8) to 57.7%+0.4 %. During UDCA treatment, the biliary content of all other bile acids was uncha nged or decreased. In conclusion, biliary enrichment of UDCA increases with incr easing dose and reaches a plateau at 22-25 mg/kg. There was no increase of toxi c hydrophobic bile acids. If biliary enrichment of UDCA represents the decisive factor for its clinical effect, it seems likely that UDCA doses of up to 22-25 mg/kg may be more effective than lower doses.
Ursodeoxycholic acid (UDCA) has beneficial effects in cholestatic liver diseas es. Inprimary sclerosing cholangitis (PSC), there is evidence that high doses ( ±20 mg/kg) of UDCA may be more effective than average doses. Biliary enrichment of UDCA at such high doses may represent the decisive factor for its beneficial effect. Up to now it is not clear how highdose UDCA correlates with its biliary enrichment and whether bacterial degradation of large amounts of UDCA may lead to an increased bacterial formation of more toxic hydrophobic bile acids. We det ermined the biliary bile acid composition in 56 patients with PSC including 30 p atients with repeat bile samples treated with various doses of UDCA. At a UDCA d ose of 10-13 mg/kg/d (n = 18) biliary UDCA represented 43.1%+0.3%(mean +SD) of total bile acids; at a UDCA dose of 14-17 mg/kg (n = 14), its biliary conte nt increased to 46.9%+0.3%, at 18-21 mg/kg (n = 34) to 55.9%+0.2%, at 22 -25 mg/kg (n = 12) to 58.6%+2.3%, and at 26-32 mg/kg (n = 8) to 57.7%+0.4 %. During UDCA treatment, the biliary content of all other bile acids was uncha nged or decreased. In conclusion, biliary enrichment of UDCA increases with incr easing dose and reaches a plateau at 22-25 mg/kg. There was no increase of toxi c hydrophobic bile acids. If biliary enrichment of UDCA represents the decisive factor for its clinical effect, it seems likely that UDCA doses of up to 22-25 mg/kg may be more effective than lower doses.
