Polymorphism of dextromethorphan oxidation in a French population.

Abstract

Genetically-controlled drug oxidation capacity was studied using dextromethorphan, an anti-tussive drug, as the test compound in 103 healthy white French subjects (61 males and 42 females). Phenotyping was performed using the metabolic ratio (MR) calculated as MR = 0-10 h urinary output of dextromethorphan/0-10 h urinary output of dextrorphan, after oral administration of 40 mg (113.6 ,umol) of dextromethorphan hydrobromide. The log MR was bimodally distributed: 99 subjects (96.1%) were phenotyped as extensive metabolizers; they had a log MR between -3.1 and -1.1, a urinary output of dextromethorphan below 5 p,mol 10 h-1 and a urinary output of dextrorphan above 20 ,umol 10 h-1.Four subjects (3.9%) were phenotyped as poor metabolizers; they had a log MR between -0.5 and +0.7, a urinary output of dextromethorphan above 5 ,umol 10 h' and a urinary output of dextrorphan below 20 ,umol 10 h-1.

Extensive oxidative metabolism of dextromethorphan in patients with almitrine neuropathy.

“…Drug oxidation phenotyping with dextromethorphan is in complete concordance with results of phenotyping with debrisoquine (Schmid et al, 1985). Dextromethorphan, an antitussive drug, has the advantages over debrisoquine of being ubiquitously available and innocuous (Schmid et al, 1985;Larrey et al, 1987).…”

“…The results were compared with those obtained in a control population of 103 healthy white French individuals (Larrey et al, 1987), using the X2_test.…”

“…Oxidator phenotyping was performed using dextromethorphan as described recently (Schmid et al, 1985;Larrey et al, 1987). The rate of O-demethylation of dextromethorphan to dextrorphan, its main metabolite, is highly correlated with that of debrisoquine 4-hydroxylation (Kupfer et al, 1984).…”

“…Subjects with a MR above 0.3 were assigned as having the poor metabolizer phenotype and subjects with a MR below 0.3 as having the extensive metabolizer phenotype (Schmid et al, 1985;Larrey et al, 1987).…”

“…0-10 h urinary output of unchanged dextromethorphan 0-10 h urinary output of dextrorphan Dextromethorphan and dextrorphan were measured in urine as described by Larrey et al (1987).…”