Influence of stable, long-term treatment with phenobarbital on the activity of serum alanine aminotransferase and γ-glutamyltransferase

Abstract

Phenobarbital, a long-acting barbiturate, is generally considered to be a fairly safe and effective drug; however, hepatotoxicity is an infrequent but potentially fatal adverse effect and there is little information on the serum activity of liver enzymes in patients on stable, long-term monotherapy. The serum activity of alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) are measured along with phenobarbital as part of the routine biochemical measurement in 128 consecutive adult out-patients on stable, long-term phenobarbital treatment. The control population consists of 2468 consecutive out-patients matched for age and gender. The patients on long-term phenobarbital therapy had significantly higher serum activities of ALT (27 IU/L versus 23 IU/L, P<0.001) and GGT (79 IU/L versus 24 IU /L, P<0.001). The prevalence of subjects with abnormal GGT values, but not ALT, was significantly higher than that in the control population. No significant differences were observed in either the mean activity or the prevalence of abnormal values of ALT or GGT between patients with suboptimal and therapeutic concentrations of the drug. These results suggest that chronic phenobarbital therapy may be associated with a clinically significant elevation of serum GGT activity. If confirmed, a specific GGT reference range should be adopted. Moreover, in those patients presenting with high serum GGT activity, it would not be necessary to reduce the dosage, discontinue the drug or change to a different anti-epileptic medication.