A study of the debrisoquine hydroxylation polymorphism in a Nigerian population

Publisher Website
Google Scholar
Abstract
The guanidine-based antihypertensive drug debrisoquine is metabolized in man mainly by alicyclic oxidation to give 4-hydroxydebrisoquine, the reaction is under the control of a single autosomal gene. The metabolic oxidation of debrisoquine was studied in 123 Nigerian volunteers. All subjects excreted unchanged drug together with 5 oxidation products, i.e., 4-, 5-, 6-, 7- and 8-hydroxy-debrisoquine. The 4-hydroxylation reaction exhibits polymorphism; 10 subjects were defective in their ability to effect this reaction. 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). 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 influence aromatic hydroxylation.