Phenotype:CYP2B6 rapid metabolizer
A CYP2B6 rapid metabolizer (RM) is a person whose CYP2B6 alleles together produce greater-than-normal enzyme activity, though not as great as the ultrarapid metabolizer. It is one of the five metabolizer phenotypes assigned from CYP2B6 genotype. This page describes the rapid-metabolizer phenotype; the enzyme itself is covered at Enzyme:CYP2B6.
Genotype basis
The rapid-metabolizer phenotype is produced by a CYP2B6 diplotype that pairs one normal-function allele with one increased-function allele.
- \*4 is the increased-function allele underlying the rapid- and ultrarapid-metabolizer phenotypes. One copy alongside a normal-function allele produces the rapid metabolizer; two copies produce the ultrarapid metabolizer.
The full allele catalogue is maintained at PharmVar and described on the Enzyme:CYP2B6 page.
Population frequency
The CYP2B6 rapid-metabolizer phenotype is less common than the reduced-activity phenotypes, because the increased-function \*4 allele is less frequent than the decreased-function \*6 allele in most populations.
Clinical consequences
Efavirenz (clearance; reduced exposure). A CYP2B6 rapid metabolizer clears efavirenz faster than a normal metabolizer and reaches lower plasma concentrations. The clinically important tail of the CYP2B6 distribution is the poor-metabolizer end, where efavirenz accumulates and produces central-nervous-system toxicity; the rapid-metabolizer end raises the opposite, and less well characterised, concern of subtherapeutic exposure and a theoretical risk of inadequate virologic suppression. CPIC's efavirenz guideline addresses the genotype-to-phenotype spectrum, but the dosing evidence is strongest at the poor-metabolizer end.[1]
See also
- Enzyme:CYP2B6, the enzyme, its history, and its full substrate spectrum.
- Phenotype:CYP2B6 poor metabolizer, Phenotype:CYP2B6 intermediate metabolizer, Phenotype:CYP2B6 normal metabolizer, Phenotype:CYP2B6 ultrarapid metabolizer, the sibling phenotypes.
- Efavirenz (the principal affected medicine).
- Category:Pharmacogenomic phenotypes
References
- ↑ Desta Z, Gammal RS, Gong L, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2B6 and Efavirenz-Containing Antiretroviral Therapy. Clinical Pharmacology and Therapeutics. 2019 Oct;106(4):726-733. PMID: 31006110.