ASSOCIATION BETWEEN CYP2C19 GENOTYPE AND PROGUANIL OXIDATIVE POLYMORPHISM

Aims To examine the relationship between proguanil metabolism and the number of mutations in CYP2C19 by comparing the CYP2C19 genotype and p roguanil phenotype of 10 subjects. Methods Partial clearance and urina ry metabolic ratio data were obtained from a previous study of 10 subj ects [5]. Analysis of CYP2C19 genotypes was performed using PCR amplif ication followed by restriction endonuclease digestion of genomic DNA from a blood sample. Results The intrinsic partial clearance of PG to CG ranged from 0.41-10.11 h(-1), and was related to the number of func tional CYP2C19 alleles present. Genotypic PMs had metabolic ratios >13 , while genotypic heterozygote EMs had metabolic ratios <9. Conclusion s Proguanil may be a suitable phenotyping probe for the CYP2C19 geneti c polymorphism, however the exact antimode of the urinary metabolic ra tio chosen to separate poor and extensive metabolisers needs further i nvestigation.