Evaluation of dextromethorphan N-demethylation activity as a biomarker for cytochrome P450 3A activity in man

The present study evaluates the usefulness of dextromethorphan N-demethylation activity indices to reflect cytochrome P450 (CYP) 3A activity in man. Indices of dextromethorphan N-demethylation activity were categorized as N1=3-methoxymorphinan/dextromethorphan, N2=3-hydroxymorphinan/dextrorphan, N3=(3-methoxymorphinan + 3-hydroxymorphinan)/(dextromethorphan + dextrorphan). Two mg of midazolam were administered orally to 22 Japanese male volunteers, and midazolam clearance determined. Thirty mg of dextromethorphan were also orally administered to these volunteers and N1, N2 and N3 indices determined by 12 hr urine collection. Results showed N2 and N3 were highly correlated (r>0.99, P<0.001), and significantly correlated to oral midazolam clearance (r=0.45, P<0.05); suggesting that N2 and N3 are more suitable than N, when using dextromethorphan as an index of individual CYP3A activity.