Monograph: |
Chenodeoxycholic Acid
A white or almost white powder. Very slightly soluble in wa-
ter; freely soluble in alcohol: soluble in acetone: slightly sol-
uble in dichloromethane.
Adverse Effects
Chenodeoxycholic acid may cause diarrhoea, especially at
the start of treatment, and pruritus. A transient rise in liver-
function test values and hypercholesterolaemia (low-density
lipoprotein) have been reported.
Chenodeoxycholic acid is embryotoxic in some animals.
Precaution"
Chenodeoxycholic acid should not be administered to pa-
tients with chronic liver disease, peptic ulcers, or inflammato-
ry bowel disease. It is ineffective for the dissolution of
calcified and pigment gallstones and is of no value in patients
without a patent and functioning gallbladder. Its use should be
avoided in pregnancy.
Interactions
Chenodeoxycholic acid should not be used with drugs, such
as oestrogenic hormones, that increase bile cholesterol. Con-
comitant administration with bile-acid binding drugs includ-
ing antacids, charcoal, and cholestyramine should be avoided
since this may reduce the effectiveness of therapy with chen-
odeoxycholic acid.
Pharmacokinetics
Chenodeoxycholic acid is absorbed from the gastro-intestinal
tract and undergoes first-pass metabolism and enterohepatic
recycling. It is partly conjugated in the liver before being ex-
creted into the bile and under the influence of intestinal bac-
teria the free and conjugated forms undergo 7a-
dehydroxylation to lithocholic acid some of which is excreted
directly in the faeces and the rest absorbed mainly lo be con-
jugated and sulphated by the liver before excretion in the fae-
ces. Chenodeoxycholic acid also undergoes epimerisation to
ursodeoxycholic acid.
Uses and Administration
Chenodeoxycholic acid is a naturally occurring bile acid . When
given by mouth it reduces hepatic synthesis of
cholesterol and provides additional bile salts to the pool avail-
able for solubilisation of cholesterol and lipids. It is used for
the dissolution of cholesterol-rich gallstones in pa-
tients with a functioning gallbladder.
Chenodeoxycholic acid is given by mouth in usual doses of
10 to 15 mg per kg body-weight daily in a single dose given
at bedtime or in divided doses: obese patients may require
doses of up to 20 mg per kg daily. The daily dose may be
divided unequally and the larger dose given before bedtime to
counteract the increase in biliary cholesterol concentrations
seen overnight.
Chenodeoxycholic acid is also used in combination with ur-
sodeoxycholic acid in the management of gallstones and low-
er doses of 5 to 7.5 mg per kg daily may then be given.
Treatment may need to be given for up to 2 years, depending
on the size of the stone. It should be continued for about 3
months after radiological disappearance of the stones.
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