Phenotype:CYP2B6 ultrarapid metabolizer

A CYP2B6 ultrarapid metabolizer (UM) is a person whose CYP2B6 alleles together produce the highest level of enzyme activity in the phenotype scale, above the rapid metabolizer, normal metabolizer, intermediate metabolizer, and poor metabolizer. This page describes the ultrarapid-metabolizer phenotype; the enzyme itself is covered at Enzyme:CYP2B6.

Genotype basis

The ultrarapid-metabolizer phenotype is produced by a CYP2B6 diplotype carrying two increased-function alleles, typically \*4/\*4. The full allele catalogue is maintained at PharmVar and described on the Enzyme:CYP2B6 page.

Population frequency

The CYP2B6 ultrarapid-metabolizer phenotype is uncommon in all well-studied populations, because it requires two copies of the relatively infrequent increased-function \*4 allele.

Clinical consequences

Efavirenz (clearance; reduced exposure). A CYP2B6 ultrarapid metabolizer clears efavirenz quickly and reaches the lowest plasma concentrations on the phenotype scale. The concern is the opposite of the poor-metabolizer concern: rather than central-nervous-system toxicity from accumulation, the ultrarapid metabolizer risks subtherapeutic efavirenz exposure and, in principle, inadequate virologic suppression. CPIC's efavirenz guideline maps the full genotype-to-phenotype spectrum, but it should be said plainly that the dosing evidence is far stronger at the poor-metabolizer end, where the toxicity signal is large and well documented, than at the ultrarapid end, where the clinical data are thinner.

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 rapid metabolizer, the sibling phenotypes.
• Efavirenz (the principal affected medicine).
• Category:Pharmacogenomic phenotypes