Therapeutic area: depression

Cytochrome P450 3A4 (CYP3A4)/ CYP 3A5 Genotyping

General Use: 

CYP3A4 is a liver enzyme that, in concert with CYP3A5, metabolizes approximately 50% of medications, including many of the statins, benzodiazepines, antibiotics, and antipsychotics. Detecting variants of the CYP3A4 gene that cause altered enzymatic activity can identify patients who may be at increased risk of having adverse drug reactions while taking standard dosages of 3A4 substrates. Roughly 4-10% of the general population possesses inherited differences in 3A4 that cause decreased metabolism. These Decreased Metabolizers may be at increased risk for dose-dependent side effects to drugs normally inactivated by 3A4.

CYP3A5 is a liver enzyme that, in concert with CYP3A4, metabolizes approximately 50% of medications, including many of the statins, benzodiazepines, antibiotics, and antipsychotics. Detecting variants of the CYP3A5 gene that cause altered enzymatic activity can identify patients who may be at increased risk of having adverse drug reactions while taking standard dosages of 3A5 substrates. More than half of the general population (60-80%) possesses inherited differences in 3A5 that cause decreased metabolism. These Decreased Metabolizers may be at increased risk for dose-dependent side effects to drugs normally inactivated by 3A5.

Limitations: 

Other variants of the CYP3A4 gene that are not detected in this assay may influence drug metabolism. CYP3A4 metabolic capacity is also influenced by concomitant medications, inhibitors, inducers, diet and various disease states. All factors should be considered as part of the overall patient management strategy.

Methodology: 

Real-time polymerase chain reaction with fluorescence detection.

Analytes Detected: 

CYP450 3A4 Analytes Detected:
*1B (-392A>G), *2 (15713T>C), *3 (23171T>C), *12 (21896C>T), *17 (15615T>C)

CYP450 3A5 Analytes Detected:
*1D (31611C>T), *6 (14690G>A), *2 (27289C>A), *7 (27131_27132insT), *3 (6986A>G), *8 (3699C>T), *3B (3709_3710insG), *9 (19386G>A)