A prospective, randomized trial of phenytoin in nonepileptic subjects with reduced HDL cholesterol

Abstract

Observational studies have demonstrated a positive association between phenytoin use and HDL cholesterol (HDL-C). Our goal was to determine whether phenytoin raises HDL-C in nonepileptic subjects at risk for coronary artery disease. We performed a double-blind, placebo-controlled, parallel-group study in 41 subjects with reduced levels of HDL-C. Subjects were placed on an American Heart Association Step I diet and were randomized to receive either phenytoin or placebo for 3 months. Serum levels of phenytoin were monitored and adjusted to between 7.5 and 15 μg/mL. Fasting levels of lipids and lipoproteins were determined twice at baseline (weeks -2 and 1) and during the treatment phase of the study (weeks 11 and 12). Compared with dietary baseline, phenytoin-treated subjects experienced significant paired percent increases in total HDL-C (12.4%; P