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2918081 
Journal Article 
Adverse effects of phenobarbital on corticosteroid metabolism in patients with bronchial asthma 
Brooks, SM; Werk, EE; Ackerman, SJ; Sullivan, I; Thrasher, K 
1972 
1 
New England Journal of Medicine
ISSN: 0028-4793
EISSN: 1533-4406 
IPA/72/64007 
Engl 
REF 16 
1125-1128 
English 
IPA COPYRIGHT: ASHP The effects of phenobarbital therapy on plasma kinetics of labeled dexamethasone were investigated in 11 asthmatic patients. The patients received 120 mg. of phenobarbital given in 4 divided daily doses. Phenobarbital caused a mean decrease in half-life of 117 minutes (-44%) and an increase in metabolic clearance rate of 272 liters per day (+88%). 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 5 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.