3,4-Dehydrodebrisoquine, a novel debrisoquine metabolite formed from 4-hydroxydebrisoquine that affects the CYP2D6 metabolic ratio.
1. The metabolic oxidation of debrisoquine has been studied in a group of 123 Nigerian volunteers. 2. All subjects excreted unchanged drug together with five oxidation products, namely, 4-, 5-, 6-, 7- and 8-hydroxy-debrisoquine. 3. The 4-hydroxylation reaction exhibits polymorphism; ten subjects were defective in their ability to effect this reaction. 4. The incidence (q) of the allele governing impaired 4-hydroxylation (DL) among Nigerians was calculated as being 0.28 (95% confidence limit of 0.20-0.37). 5. An association was demonstrated between the ability to effect 4-hydroxylation and 6- and 7-hydroxylation of debrisoquine, suggesting that the alleles controlling alicyclic oxidation also influence aromatic hydroxylation.