ASSESSMENT OF DOXYLAMINE INFLUENCE ON MIXED-FUNCTION OXIDASE ACTIVITYUPON MULTIPLE-DOSE ORAL-ADMINISTRATION TO NORMAL VOLUNTEERS

The primary purpose of this study was to assess the influence of doxyl amine and phenabarbital on antipyrine/metabolites pharmacokinetics and 6 beta-hydroxycortisol urinary excretion. This study was conducted in 48 healthy male human volunteers (16 per treatment group) using a par allel study design. Treatment groups consisted of 12.5 mg of doxylamin e succinate, placebo, or 30 mg of phenobarbital administered orally ev ery 6 h for 17 days. Results indicate that no statistically significan t 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 45 mL/h/kg) and nonrenal (35 versus 44 mL/h/kg) clearances and 6 beta-hydroxycortisol excretion (338 versus 529 mu g) and a significant decrease in the ter minal exponential halt-life (11 versus 9 h) of antipyrine were observe d.