Pharmacokinetics and polymorphic oxidation of dextromethorphan in a Japanese population.

N Nagai, T Kawakubo, F Kaneko, M Ishii, R Shinohara, Y Saito, H Shimamura, A Ohnishi, H Ogata

Index: Biopharm. Drug Dispos. 17(5) , 421-33, (1996)

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Abstract

The plasma concentration and cumulative urinary excretion over 34 h of dextromethorphan, free and conjugated dextrorphan, and 3-hydroxymorphinan were determined in seven healthy Japanese subjects after oral administration of 30 mg dextromethorphan hydrobromide. Conjugated metabolites were extensively present, whereas no detectable dextromethorphan or free metabolites were observed in the plasma of any subject. On average, 72% of the dose was excreted in urine within 34 h. This was detected mainly as conjugated metabolites with only slight traces of dextromethorphan and free metabolites. From the time-courses of the metabolic ratio (the ratio of urinary output of dextromethorphan to dextrorphan), the metabolic ratios seemed to become constant 7.5 h after oral administration. Phenotyping was performed using metabolic ratios in 75 unrelated healthy Japanese subjects (43 males and 32 females). The logarithmic metabolic ratio was bimodally distributed and one subject (1.3%) was identified as a poor metabolizer.