Abstract
Aims To examine the relationship between proguanil metabolism and the number of mutations in CYP2C19 by comparing the CYP2C19 genotype and proguanil phenotype of 10 subjects.
Methods Partial clearance and urinary metabolic ratio data were obtained from a previous study of 10 subjects [ 5]. Analysis of CYP2C19 genotypes was performed using PCR amplification followed by restriction endonuclease digestion of genomic DNA from a blood sample.
Results The intrinsic partial clearance of PG to CG ranged from 0.41–10.1l h−1, and was related to the number of functional CYP2C19 alleles present. Genotypic PMs had metabolic ratios >13, while genotypic heterozygote EMs had metabolic ratios <9.
Conclusions Proguanil may be a suitable phenotyping probe for the CYP2C19 genetic polymorphism, however the exact antimode of the urinary metabolic ratio chosen to separate poor and extensive metabolisers needs further investigation.
Keywords: proguanil, metabolic ratio, intrinsic clearance, CYP2C19, mutant alleles
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