Phenotype:CYP2B6 intermediate metabolizer

A CYP2B6 intermediate metabolizer (IM) is a person whose CYP2B6 alleles together produce reduced, but not substantially absent, enzyme activity. It is one of the five metabolizer phenotypes assigned from CYP2B6 genotype, sitting between the poor metabolizer and the normal metabolizer, with the rapid metabolizer and ultrarapid metabolizer above. This page describes the intermediate-metabolizer phenotype; the enzyme itself is covered at Enzyme:CYP2B6.

The intermediate metabolizer is a milder version of the poor metabolizer: efavirenz and the other CYP2B6-cleared medicines are cleared slowly and accumulate, but to a lesser degree.

Genotype basis

The intermediate-metabolizer phenotype is produced by a CYP2B6 diplotype that pairs one normal-function allele with one decreased-function or no-function allele, most often a diplotype carrying a single \*6 allele (such as \*1/\*6) or a single \*18 allele. The full allele catalogue is maintained at PharmVar and described on the Enzyme:CYP2B6 page.

Population frequency

Because the \*6 allele is common in all well-studied populations and very common in African and African-ancestry populations, the CYP2B6 intermediate-metabolizer phenotype is one of the more frequently encountered metabolizer phenotypes for any drug-metabolizing enzyme.

Clinical consequences

Efavirenz (clearance; modestly raised exposure). A CYP2B6 intermediate metabolizer reaches higher efavirenz plasma concentrations than a normal metabolizer, though less markedly than a poor metabolizer, and carries an intermediate risk of efavirenz central-nervous-system side effects. CPIC's efavirenz guideline addresses the intermediate metabolizer explicitly, with a dose recommendation that sits between standard dosing and the reduced dose advised for poor metabolizers.

Methadone and cyclophosphamide. For methadone, an intermediate metabolizer reaches modestly higher exposures; for cyclophosphamide, the prodrug that CYP2B6 bioactivates, an intermediate metabolizer activates the medicine somewhat more slowly than a normal metabolizer. Neither is currently the subject of genotype-guided dosing.

See also

• Enzyme:CYP2B6, the enzyme, its history, and its full substrate spectrum.
• Phenotype:CYP2B6 poor metabolizer, Phenotype:CYP2B6 normal metabolizer, Phenotype:CYP2B6 rapid metabolizer, Phenotype:CYP2B6 ultrarapid metabolizer, the sibling phenotypes.
• Efavirenz, Methadone (representative affected medicines).
• Category:Pharmacogenomic phenotypes