Cytochrome P450 3A5 (CYP3A5) Genotyping

Medical Test

• Determining therapeutic strategy for therapeutics that are metabolized by the CYP3A5 gene product (antidepressant and other metabolized drugs)
• Monitor and manage tacrolimus and statin drug therapy
• Monitor and manage pain management drug therapy
• As an aid in therapy of prostate cancer and leukemias

• If genotype CYP3A5 1/1 or 1/3 or *1 other alleles are detected, this would be reported as normal to intermediate metabolizer
• If genotype CYP3A5 3/3 is detected, or if CYP3A5 *1 allele is NOT detected, this would be reported as a poor metabolizer

The following is a list of major therapeutic classes with drugs that are substantially metabolized by CYP3A.

Statins: atorvastatin, simvastatin, lovastatin.

Calcium channel blockers: nifedipine, verapamil, nicardipine, felodipine, nisoldipine.

Antiplatelets: clopidogrel, prasugrel, ticagrelor, cilostazol.

Antiarrhythmics: amiodarone, quinidine, disopyramide, lidocaine.

Example of angina treatments: ranolazine.

Angiotensin II Inhibitors: losartan.

Anticoagulants: rivaroxaban, apixaban.

The following is a list of major inhibitors that compete with other drugs for a particular enzyme thus affecting the optimal level of metabolism of the substrate drug which in many cases affect the individual's response to that particular medication, e.g. making it ineffective.

A Strong inhibitor is one that causes a > 5-fold increase in the plasma AUC values or more than 80% decrease in clearance. This include: indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole,nefazodone, saquinavir, telithromycin

A Moderate inhibitor is one that causes a > 2-fold increase in the plasma AUC values or 50-80% decrease in clearance. This include: aprepitant, erythromycin, fluconazole, grapefruit juice, verapamil, diltiazem

A Weak inhibitor is one that causes a > 1.25-fold but < 2-fold increase in the plasma AUC values or 20-50% decrease in clearance such as cimetidine, amiodarone, chloramphenicol, boceprevir, ciprofloxacin, delaviridine, diethyl, dithiocarbamate, fluvoxamine, gestodene, imatinib, mibefradil, mifepristone, norfloxacin, norfluoxetine, starfruit, telaprevir, voriconazole

CYP3A5 *1/*1 (Normal metabolizer)

Whole blood collected in lavender top tube (EDTA) or any anticoagulant collection devices, buccal swab, saliva. 

Stability

• Ambient: 5 days
• Refrigerated: 7 days

Therapeutic drug monitoring is the standard of care for monitoring patients on tacrolimus. Drug toxicity tests and clinical assessments are recommended for other drugs; other CYP enzymes such as CYP2D6, CYP2C19, and CYP2C9.

3-5 days.