Short animated video to illustrate essential pharmacogenetic features with respect to CYP2C19.
Originally identified as mephenytoin hydroxylase, but eventually re-named CYP2C19. The metabolism of mephenytoin by CYP2C19 stereoselectively favours the S-enantiomer. Consequently, if the racemic mixture is administered, the S/R ratio of mephenytoin may be used as the metabolic ratio for phenotyping.
CYP2C19 is genetically polymorphic. Three types of alleles are identifiable - the normal wildtype allele, the loss of function alleles (mainly *2 and *3) and the increased activity allele (*17).
Four main phenotypes are recognizable - extensive metabolizer,
EM, (homozygous wild-type), poor metabolizer, PM, (homozygous or compound homozygous for loss of function allele, intermediate metabolizer, IM, (heterozygous for wildtype or *17 with loss of function allele), ultrarapid metabolizer, UM, (homozygous or heterozygous *17).
There is a reasonable genotype-phenotype correlation, with the major difference between extensive metabolizers and poor metabolizers. The ultra-rapid metabolizer pheotype may be identified, but overlaps completely with the extensive metabolizers. The difference is not clinically significant.
Common substrates include:
antiplatelet agents - clopidogrel
proton pump inhibitors - e.g. omeprazole
antiepileptics - e.g. mephenytoin, phanytoin
For more information on CYP2C19 phenotypes and clopidogrel dosing, please view:
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