Pheno- or genotype for the CYP2C19 drug metabolism polymorphism: the influence of disease.

A genotyping approach for pharmacogenes such as CYP2C19 is often advocated to "personalise therapy", since individuals with the homozygous null allele genotype are poor metabolisers (PM) of many drugs. The genotype-phenotype relationship is a validated approach for S-mephenytoin, proguanil and omeprazole in young, healthy populations. However, this relationship may not be valid in patients with diseases such as cancer and congestive heart failure, or in old age. The high phenotypic discordance in the genotypic EM group means that in many clinical situations the true number of CYP2C19 poor metabolisers may be under-estimated if only genotypic approaches are used.