- CYP3A4 is responsible for the metabolism of more than 50% of medicines.
- CYP3A4 activity is absent in new-borns but reaches adult levels at around one year of age.
- Women have higher CYP3A4 activity than men.
Major Drugs
| Effect | Strong | Moderate | Weak |
|---|---|---|---|
| Inhibitor | ritonavir, grapefruit juice, azoles, (posaconazole, voriconazole, ketoconazole, itraconazole) | aprepitant, ciprofloxacin, crizotinib, cyclosporine, diltiazem, dronedarone, erythromycin, fluconazole, fluvoxamine, imatinib, isavuconazole, verapamil | cilostazol, cimetidine, clotrimazole, ranitidine, ranolazine, ticagrelor |
| Inducer | carbemazepine, phenytoin, fosphenytoin, phenobarbital, rifampin, enzalutamide | bosentan, dabrafenib, efavirenz | -- |
| Note: | |||
| - Strong, moderate, and weak inhibitors are drugs that increase the AUC of sensitive index substrates of a given metabolic pathway ≥5-fold, ≥2 to <5-fold, and ≥1.25 to <2-fold, respectively. | |||
| - Strong, moderate, and weak inducers are drugs that decreases the AUC of sensitive index substrates of a given metabolic pathway by ≥80%, ≥50% to <80%, and ≥20% to <50%, respectively. |
Inhibitors
Think of: azoles, ritonavir, FLQ, CNI, nonDHP-CCB, macrolides, H2RBs.
Inducers
Think of: AEDs, rifampin, small molecule chemotherapies.
References
- Drug Metabolism - The Importance of Cytochrome P450 3A4
- Drug Development and Drug Interactions | Table of Substrates, Inhibitors and Inducers