Determination of dextromethorphan metabolizer phenotype in healthy volunteers.

The dextromethorphan metabolizer phenotype in 450 healthy volunteers (299 men, 151 women) was determined after oral administration of a 15 mg dose. In 8 h-postdose urine samples the ratio of dextrorphan (DOP) to dextromethorphan (DMP) was measured by HPLC. Urinary excretion of DMP and DOP within 8 h after the dose varied greatly between individuals, ranging from 0-11% and 0.04-100% of dose, respectively. In 143 test subjects the fraction of the dose of DMP in urine was below the detection limit. In the remaining 307 volunteers the metabolic ratio (MR) of DOP to DMP varied from 0.07 to 2906. In 404 test subjects the MR was greater than 10 and they were classified as extensive metabolizers (90% of the entire group). Of the entire group 5% had MRs of 1-10 and less than 1, respectively. Depending on the limit for classification of poor metabolizers, their frequency was 5-10% in the Caucasian population studied. The present data are in agreement with previous findings that the oxidative metabolic polymorphisms of debrisoquin and DMP co-segregate; the frequency of the PM phenotype of dextromethorphan in Caucasian populations varies between 5 and 10%.