Dextromethorphan O-demethylation and dextrorphan glucuronidation in a French population.
The dextromethorphan (DMP) O-demethylation and the dextrorphan (DRP) glucuronidation distributions were studied in 120 French Caucasian subjects. After a single 25 mg DMP oral administration, DMP, free and total DRP concentrations were measured in 8h-urine collection, using an HPLC technique with fluorescent detection. The DMP and free DRP concentrations ratio, in log form, was used to estimate the oxidative demethylation phenotype of the subjects. Two different populations were found. The first one consisted of the extensive metabolizers (90.8%, 95% confidence interval from 85.6 to 95.9%) and the second one consisted of poor metabolizers (9.2%, 95% confidence interval from 4.0 to 14.4%). The antimode value of the distribution was estimated at approximately 0.7 corresponding to a ratio of 5. Moreover, this ratio was compared to the DMP and total DRP concentrations ratio, usually defined to DMP O-demethylation phenotyping. On the other hand, the glucuronide DRP concentration was calculated by subtracting the free DRP concentration from the total DRP concentration. Consequently, the free DRP and glucuronide DRP concentrations ratio was also used to estimate the DRP glucuronidation in the present population. This ratio in log form reflected the UDP-glucuronyltransferase(s) capacity(ies). This log ratio appeared to be normally distributed in the population studied. These results show that log DMP/free DRP ratio can be used, as well as log DMP/total DRP ratio, to determine the oxidative phenotype of subjects and that the DRP conjugation does not exhibit any apparent genetic polymorphism.
Duché
J C
JC
Laboratoire Hospitalo-Universitaire de Pharmacologie, Centre Hospitalier Intercommunal, Créteil, France.
Quérol-Ferrer
V
V
Barré
J
J
Mésangeau
M
M
Tillement
J P
JP
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000652:urine*; D003915:Dextromethorphan / Q000493:pharmacokinetics*; D003917:Dextrorphan / Q000652:urine*; D005260:Female; D005602:France; D005965:Glucuronates / Q000652:urine*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010090:Oxidoreductases, O-Demethylating / Q000652:urine*; D011110:Polymorphism, Genetic
D005965:Glucuronates; D003917:Dextrorphan; D003915:Dextromethorphan; D003577:Cytochrome P-450 Enzyme System; D010090:Oxidoreductases, O-Demethylating; C052861:dextromethorphan O-demethylase