From the Guidelines
No, statins are not metabolized by the cytochrome P450 2D6 (CYP2D6) enzyme. The primary form of drug metabolism for most statins occurs through CYP450 enzymes, with the most prevalent CYP450 enzyme subcategories for statin metabolism being the 3A4 and 2C9 enzyme systems 1. Simvastatin and lovastatin undergo significant CYP3A4 metabolism, and atorvastatin undergoes a lesser amount as one of its minor metabolic pathways, while fluvastatin, pitavastatin, and rosuvastatin require CYP2C9 1.
Key Points to Consider
- The CYP2D6 enzyme is not a primary metabolic pathway for any statin medication
- Clinicians should be aware of the potential for drug interactions with statins that are metabolized by CYP3A4, such as increased risk of myopathy with certain antifungals, antibiotics, and grapefruit juice
- CYP2D6 inhibitors, such as fluoxetine or paroxetine, are not expected to significantly affect statin metabolism
- Understanding the metabolic pathways of statins can help clinicians avoid potentially harmful drug interactions when prescribing statins alongside other medications 1.
Implications for Clinical Practice
- When prescribing statins, clinicians should consider the potential for drug interactions with other medications that may inhibit or induce CYP3A4 or CYP2C9
- Patients taking statins should be monitored for signs of myopathy or other adverse effects, particularly when taking medications that may interact with their statin
- Clinicians should choose statins that are less likely to interact with other medications, such as those that are not extensively metabolized by CYP3A4 or CYP2C9 1.
From the Research
Statin Metabolism
- The metabolism of statins is primarily governed by the cytochrome P450 (CYP) system, with specific enzymes playing a role in the metabolism of different statins 2, 3, 4, 5, 6.
- CYP3A4 is a key enzyme involved in the metabolism of several statins, including atorvastatin, simvastatin, and lovastatin 2, 3, 4, 6.
- Other statins, such as pravastatin and rosuvastatin, are not significantly metabolized by CYP3A4 and have a lower potential for drug interactions 4, 5.
- CYP2D6 is not mentioned as a primary enzyme involved in the metabolism of statins in the provided studies 2, 3, 4, 5, 6.
Specific Statin Metabolism
- Atorvastatin is metabolized by CYP3A4, with a high intrinsic clearance value of 3700 µl/min per milligram in human liver microsomes (HLMs) 6.
- Simvastatin is also metabolized by CYP3A4, with an intrinsic clearance value of 7400 µl/min per milligram in HLMs 6.
- Pitavastatin has a slower metabolism, with an intrinsic clearance value of 20-840 µl/min per milligram in HLMs 6.
- Rosuvastatin is not significantly metabolized by CYP3A4 and has a low potential for drug interactions 5.