Phenotype:CYP2C19 normal metabolizer

A CYP2C19 normal metabolizer (NM) is a person whose CYP2C19 alleles together produce the typical, reference level of enzyme activity. It is one of the five metabolizer phenotypes assigned from CYP2C19 genotype, with the poor metabolizer and intermediate metabolizer below it and the rapid metabolizer and ultrarapid metabolizer above. This page describes the normal-metabolizer phenotype; the enzyme itself is covered at Enzyme:CYP2C19.

The normal metabolizer is the reference phenotype. The standard, label-recommended doses of CYP2C19-affected medicines, including the standard use of clopidogrel after percutaneous coronary intervention, are calibrated to normal-metabolizer populations. For a normal metabolizer, CYP2C19 genotype is not a reason to depart from standard treatment.

Genotype basis

The normal-metabolizer phenotype is produced by the \*1/\*1 diplotype, two normal-function alleles. The full allele catalogue is maintained at PharmVar and described on the Enzyme:CYP2C19 page.

A note on the terminology: as with the other harmonized phenotype scales, the normal metabolizer was formerly called the extensive metabolizer (EM), a label changed because "extensive" was read as "greater than normal" when it meant "typical".

Population frequency

The CYP2C19 normal-metabolizer phenotype is found in roughly 35 to 45% of most populations. Unlike CYP2D6, where the normal metabolizer is a clear majority, CYP2C19 spreads its population more evenly across the phenotype range, because both the loss-of-function \*2 and \*3 alleles and the gain-of-function \*17 allele are common.

Clinical significance

For a CYP2C19 normal metabolizer, standard dosing of CYP2C19-affected medicines applies, and no genotype-based adjustment is indicated. Clopidogrel can be used at its standard dose with the expected antiplatelet effect.

Two caveats apply, as for any normal-metabolizer phenotype. First, a normal metabolizer is readily phenocopied: co-prescription of a strong CYP2C19 inhibitor (fluvoxamine, fluoxetine, omeprazole) converts the patient, functionally, into an intermediate or poor metabolizer for the duration of the inhibition. The clopidogrel-and-omeprazole combination is the interaction to watch. Second, normal-metabolizer status addresses CYP2C19 genotype only; it says nothing about the other determinants of a medicine's effect.

See also

• Enzyme:CYP2C19, the enzyme, its history, and its full substrate spectrum.
• Phenotype:CYP2C19 poor metabolizer, Phenotype:CYP2C19 intermediate metabolizer, Phenotype:CYP2C19 rapid metabolizer, Phenotype:CYP2C19 ultrarapid metabolizer, the sibling phenotypes.
• Category:Pharmacogenomic phenotypes