ISSN:
1573-2568
Keywords:
23-methyl-ursodeoxycholic acid
;
bile flow
;
liver biotransformation
;
critical micellar concentration
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract 3α,7β-Dihydroxy-23-methyl-5β-cholan-24-oic acid (MUDCA) and its two diastereoisomers, α- and β-MUDCA, were infused intraduodenally in biliary fistula hamsters in order to evaluate the effect on bile flow and their hepatic biotransformation processes compared with the natural analog ursodeoxycholic acid (UDCA). In addition, the corresponding glycine conjugates were compared. The bile acids were administered at different doses (0.7–6 μmol/min/kg) over periods of 90 min. The results indicate that the racemic mixture exhibits a potent choleretic effect at both low and high doses, while the two individual diastereoisomers show this effect only at high doses. The presence of a C-23 methyl group in the side chain prevents hepatic amidation and alternative conjugations occur, such as glucuronidation, in order to facilitate their biliary secretion. Biotransformation of the methyl derivatives of UDCA occurred mainly by conversion to more polar glucuronide conjugates. There was little alteration to the molecule and, unlike UDCA, very little amidation occurred. These data indicate that the presence of a C-23 methyl group prevents the usual side-chain amidation common to the most naturally occurring bile acids and that glucuronidation is a requisite for efficient biliary excretion.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01296441
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