Pain Panel — CYP2D6, CYP2C19, CYP3A4 and CYP3A5
These pharmacogenetic tests aid the physician in determining the appropriate pain medicine and dose for patientswho may have a genetic risk for altered drug metabolism. The proportion of patients who respond positively to theirmedications is, on average, only approximately 50% (ranging from 25-60%).
When drugs metabolized by the Cytochrome P450 (CYP) enzymes are administered, variant genotypes are associated with increased potential for Adverse Drug Reactions (ADR), therapeutic failure and risk of drug interactions. A prospective study of US hospitals estimated that 106,000 Americans die annually from ADR.2
Patient phenotype may apply clinically to drug and dose selection decisions based on whether a drug is activated or inactivated by the P450 enzyme.
Pharmacogenetic testing can help determine the appropriateness and dosage of many of the most commonly prescribed drugs including:
- Beta Blockers
Real Time PCR with TaqMan Chemistry
There are four types of drug metabolizers:
- Poor metabolizers have very low levels of enzyme activity and process certain medications at a lower-thannormal rate. For drugs that are eliminated following CYP metabolism, poor metabolizers are at risk for toxicity because the patient cannot dispel the medication quickly enough. If the drug is a pro-drug or inactive when taken and activated by metabolism, then the drug may not be effective for poor metabolizers. An alternate drug treatment may be necessary for a poor metabolizer.
- Intermediate metabolizers have moderately decreased metabolic activity. Intermediate metabolizers also inactivate drugs more slowly, between an extensive and poor rate of metabolism. These patients may require lower than average drug dose for optimal therapeutic response. However, for prodrugs that require activation by a CYP enzyme, intermediate metabolizers may need an increased dose or an alternative treatment.
- Extensive metabolizers are considered “normal” and are likely to have the expected response to the drug. Extensive metabolizers may use the standard dose and treatment.
- Ultra-rapid metabolizers have high levels of enzyme activity and process drugs at a higher-than-normal rate. Ultra rapid metabolizers are at increased risk of therapeutic failure due to increased drug elimination and thus may require an increased dose of drugs that are inactivated. For prodrugs, ultra rapid metabolizers may be at increased risk of drug-induced side effects due to increased exposure to active drug metabolites. Therefore ultra-rapid metabolizers may require lower than average doses for prodrugs.
Limitations The detection of genetic variants does not replace the need for therapeutic drug monitoring or other
appropriate clinical monitoring by the health care provider. Additional mutations for the tested genes that are not
described in the methodology section will not be detected. Since drug metabolism is influenced by ethnicity, diet, and other medications, these additional factors need to be considered by the health care provider. Some drugs may decrease or increase levels of specific CYPs. Combined effect of variants of CYP2D6, CYP2C19, CYP3A4 and CYP3A5 genotypes on phenotype is not well-understood.