Effect of liver disease on dextromethorphan oxidation capacity and phenotype: a study in 107 patients.
1. The O-demethylation of dextromethorphan to dextrorphan exhibits a genetically-controlled polymorphism, co-segregating with that of debrisoquine hydroxylation. Dextromethorphan has been proposed as a test compound to assess drug oxidation polymorphism. 2. We studied the effects of liver disease of varying severity on dextromethorphan oxidation capacity. Phenotyping was performed using the urinary dextromethorphan/dextrorphan metabolic ratio after oral administration of 40 mg dextromethorphan hydrobromide in 56 patients with cirrhosis and in 51 patients with moderately severe liver disease. 3. Dextromethorphan oxidation capacity was impaired in cirrhotic patients and, to lesser extent, in non cirrhotic patients, as compared with 103 control subjects. 4. The impairment in dextromethorphan oxidation induced by liver disease, was however, much less than that caused by the genetic deficiency. As a result, the prevalence of the poor metabolizer phenotype remained in the same range in patients with cirrhosis (1.8%) and with moderately severe disease (2.0%) as in controls (3.9%). 5. This observation shows that, although liver disease causes some impairment of dextromethorphan O-demethylation, this impairment is not sufficient to modify the assignment of phenotypes.
Larrey
D
D
Unité de Recherches de Physiopathologie Hépatique (INSERM U 24), Clichy, France.
Babany
G
G
Tinel
M
M
Freneaux
E
E
Amouyal
G
G
Habersetzer
F
F
Letteron
P
P
Pessayre
D
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003404:Creatinine / Q000097:blood; D003915:Dextromethorphan / Q000378:metabolism*; D003917:Dextrorphan / Q000652:urine; D005260:Female; D006801:Humans; D007981:Levorphanol / Q000031:analogs & derivatives*; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D010641:Phenotype
D003917:Dextrorphan; D007981:Levorphanol; D003915:Dextromethorphan; D003404:Creatinine