Adverse Effects of Phenobarbital on Corticosteroid Metabolism in Patients with Bronchial Asthma

Abstract

The effects of phenobarbital therapy on plasma kinetics of labeled dexamethasone were investigated in 11 asthmatic patients. Phenobarbital caused a mean decrease in half-life of 117 minutes (-44 per cent) and an increase in metabolic clearance rate of 272 liters per day (+88 per cent). Urinary radioactivity excretion rate rose, the greatest increase occurring in the unconjugated ethyl acetate fraction. Increased urinary 6-hydroxycortisol excretion supported the presence of hepatic enzyme induction. These effects were not noted in five placebo-treated patients. Three prednisone-dependent patients showed clinical worsening, deterioration of spirometric tests and increased eosinophil counts following phenobarbital. Phenobarbital withdrawal reversed these changes; reduction of prednisone dosage or discontinuation was then possible. Nonsteroid-dependent patients did not show similar changes after phenobarbital therapy. Dexamethasone and prednisone seem to be metabolized more rapidly during phenobarbital administration, resulting in lower blood levels and less physiologic activity. Thus, caution is necessary in prescribing barbiturates to asthmatic patients treated with these steroids.