OMISSION OF THE DECONJUGATION STEP IN URINE ANALYSIS AND THE UNALTERED OUTCOME OF CYP2D6 PHENOTYPING WITH DEXTROMETHORPHAN

The present study was aimed at determining whether the deconjugation s tep in chemical analysis could be omitted without altering the outcome of phenotyping CYP2D6 with dextromethorphan. This drug and its metabo lite, dextrorphan, were assayed by high-performance liquid chromatogra phy (HPLC) in urine. Urinary levels of dextromethorphan and dextrorpha n with and without enzymatic (beta-glucuronidase) treatment of urine a nd the metabolic ratios for dextromethorphan were determined in 45 sub jects. Although the enzymatic treatment did not alter the urinary conc entration of dextromethorphan in both phenotypes, it increased the uri nary concentration of dextrorphan in both poor and extensive metaboliz ers by 3.7- and 12.8-fold, respectively. A urinary unconjugated dextro methorphan/unconjugated dextrorphan metabolic ratio of 2.00 and a tota l dextromethorphan/total dextrorphan metabolic ratio of 0.30, respecti vely, identified three poor metabolizers. Enzymatic treatment decrease d the urinary antimode value. Moreover, the urinary metabolic ratio ba sed on unconjugated dextrorphan and dextromethorphan correlated well w ith that based on assay of total dextrorphan and dextromethorphan (r(s ) = 0.9458, P < 0.001). The results show that urinary analysis of dext rorphan and dextromethorphan omitting the enzymatic deconjugation step is a fast, reliable and sensitive method and could be used for studyi ng CYP2D6 type genetic polymorphism in man.