Assessment of Doxylamine Influence on Mixed Function Oxidase Activity upon Multiple Dose Oral Administration to Normal Volunteers

The primary purpose of this study was to assess the influence of doxylamine and phenobarbital on antipyrine/metabolites pharmaco-kinetics and 6β-hydroxycortisol urinary excretion. This study was conducted in 48 healthy male human volunteers (16 per treatment group) using a parallel study design. Treatment groups consisted of 12.5mg of doxylamine succinate, placebo, or 30mg of phenobarbital administered orally every 6h for 17days. Results indicate that no statistically significant differences were observed between the doxylamine and placebo groups that are indicative of enzyme induction. For the phenobarbital group, a significant increase for antipyrine total (36 versus 45mL/h/kg) and nonrenal (35 versus 44mL/h/kg) clearances and 6β-hydroxycortisol excretion (338 versus 529 µg) and a significant decrease in the terminal exponential half-life (11 versus 9 h) of antipyrine were observed.