Polymorphic Oxidation of Sparteine and Debrisoquine: Related Pharmacogenetic Entities

Abstract

A randomly selected population of 234 Ghanaian volunteers were phenotyped by administering single oral doses of debrisoquine and sparteine in a cross over study for their ability to 4-hydroxylate debrisoquine and N-oxidize sparteine. The close correlation between urinary metabolic ratios of the two drugs demonstrates that the polymorphic 4-bydroxylation of debrisoquine and N-oxidation of sparteine arc related pharmacogenetic entities in Ghanaians. Leucocyte DNA from a subset of subjects were analysed for a number of mutations in the CYP2D6 gene. Genotype was preformed using both restriction fragment length polymorphism (RFLP) assay with restriction enzyme XbaI, together with allele-specific amplification polymerase chain reaction assay. Two subjects phenotyped with both sparteine and debrisoquine as poor metabolizers (PMs) were observed to have XbaI-RFLP patterns 44/ 11.5 kb and showed the 29B mutation.