Phenobarbital Can Aggravate a Cholestatic Bile Acid Pattern in Infants with Obstructive Cholangiopathy

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Abstract
The effect of phenobarbital on urinary bile acid excretion in intrahepatic cholestasis was studied in four boys 4-43 months of age who received 10 mg/kg of body weight of phenobarbital for a period of 3 weeks-3 years. One child was observed at two different periods: with and without histologically proven cirrhosis. Before the treatment period, the infants excreted 10-fold higher amounts of bile acids in urine than healthy children. The primary bile acids predominated, and there were also increased amounts of polyhydroxylated bile acids, 3.beta.-hydroxy-5-cholenoic acid, and ketonic bile acids but small amounts of secondary bile acids. After the phenobarbital treatment, the patients further increased their urinary bile acid excretion, including all kinds of bile acids except the secondary ones. The sulfated fraction did not increases in absolute amounts, and its relative percentage decreased from a mean of 60-33%. Lver function tests results generally did not improve, although serum concentration bilirubin decreased. Most of these changes suggested a worsening of the cholestatic state after phenobarbital treatment. The results indicate that at our present state of knowledge, phenobarbital should not be given routinely to infants or children with intraheptic cholestasis.