Phenotype:CYP2B6 normal metabolizer
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A CYP2B6 normal metabolizer (NM) is a person whose CYP2B6 alleles together produce the typical, reference level of enzyme activity. It is one of the five metabolizer phenotypes assigned from CYP2B6 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:CYP2B6.
The normal metabolizer is the reference phenotype. The standard dose of efavirenz and of the other CYP2B6-affected medicines is calibrated to normal-metabolizer populations, and for a normal metabolizer CYP2B6 genotype is not a reason to depart from standard dosing.
Genotype basis
The normal-metabolizer phenotype is produced by a CYP2B6 diplotype of two normal-function alleles, typically \*1/\*1. The full allele catalogue is maintained at PharmVar and described on the Enzyme:CYP2B6 page.
Population frequency
The CYP2B6 normal-metabolizer phenotype is common but, because the reduced-function \*6 allele is so widespread, it does not dominate any population the way the normal-metabolizer phenotype dominates for some other enzymes. In African and African-ancestry populations in particular, the high \*6 frequency means a large share of the population falls into the intermediate- or poor-metabolizer phenotypes rather than the normal one.
Clinical significance
For a CYP2B6 normal metabolizer, standard dosing of CYP2B6-affected medicines applies. Efavirenz can be given at its standard dose with the expected balance of virologic efficacy and central-nervous-system tolerability.
The two standing caveats apply. A normal metabolizer can be phenocopied by a CYP2B6 inhibitor; and normal-metabolizer status addresses CYP2B6 genotype only, not the other determinants of a medicine's effect. For efavirenz specifically, even a normal metabolizer can experience central-nervous-system side effects, because the standard dose was set against a population average and individual tolerance varies for reasons beyond CYP2B6 genotype.
See also
- Enzyme:CYP2B6, the enzyme, its history, and its full substrate spectrum.
- Phenotype:CYP2B6 poor metabolizer, Phenotype:CYP2B6 intermediate metabolizer, Phenotype:CYP2B6 rapid metabolizer, Phenotype:CYP2B6 ultrarapid metabolizer, the sibling phenotypes.
- Efavirenz (the principal affected medicine).
- Category:Pharmacogenomic phenotypes