From the Guidelines
Lipophilic statins include atorvastatin, simvastatin, lovastatin, pitavastatin, and fluvastatin, which are characterized by their ability to easily cross cell membranes and the blood-brain barrier due to their fat-soluble nature. These medications work by inhibiting HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis, thereby reducing LDL cholesterol levels in the bloodstream. Unlike hydrophilic statins (such as rosuvastatin and pravastatin), lipophilic statins are metabolized primarily by the cytochrome P450 enzyme system in the liver, which can increase their potential for drug interactions, as noted in the European guidelines on cardiovascular disease prevention in clinical practice 1. This property also allows them to be distributed more widely throughout body tissues beyond the liver.
When prescribing lipophilic statins, it's essential to monitor for potential side effects such as muscle pain or weakness, as their wider tissue distribution may contribute to muscle-related adverse effects in some patients. The safety profile of statins is generally acceptable, with occasional liver dysfunction being reversible and rhabdomyolysis being rare, as reported in the European guidelines on cardiovascular disease prevention in clinical practice 1. Dosing varies by specific medication, with atorvastatin typically prescribed at 10-80 mg daily and simvastatin at 5-40 mg daily, preferably in the evening, as indicated in the acc/aha/nhlbi clinical advisory on the use and safety of statins 1.
Key considerations for prescribing lipophilic statins include:
- Monitoring for potential drug interactions, particularly with medications such as ciclosporin, macrolides, azole antifungals, calcium antagonists, protease inhibitors, sildenafil, warfarin, digoxin, nicotinic acid, and fibrates, as highlighted in the European guidelines on cardiovascular disease prevention in clinical practice 1
- Being aware of the potential for muscle-related adverse effects and taking steps to minimize this risk, such as identifying vulnerable patients and avoiding statin interactions with specific drugs, as noted in the European guidelines on cardiovascular disease prevention in clinical practice 1
- Ensuring that patients are aware of the potential drug interactions and side effects associated with lipophilic statins, as emphasized in the acc/aha/nhlbi clinical advisory on the use and safety of statins 1.
From the FDA Drug Label
Simvastatin is a white to off-white, nonhygroscopic, crystalline powder that is practically insoluble in water, and freely soluble in chloroform, methanol and ethanol
- Lipophilic statins are those that are soluble in non-polar solvents such as chloroform.
- Based on the information provided, simvastatin is a lipophilic statin because it is freely soluble in chloroform, methanol, and ethanol 2.
- Pitavastatin and pravastatin are not explicitly described as lipophilic in their respective labels, and their solubility properties do not clearly indicate lipophilicity 3 4.
From the Research
Lipophilic Statins
The following statins are classified as lipophilic:
Characteristics of Lipophilic Statins
Lipophilic statins can easily enter cells 5. They have a strong effect on lowering plasma total cholesterol and triacylglycerol, as seen with pitavastatin 6. Lipophilic statins may also have pleiotropic effects, such as decreasing inflammation and oxidative stress, regulating angiogenesis and osteogenesis, improving endothelial function and arterial stiffness, and reducing tumor progression, as reported for pitavastatin 6, 7.
Pharmacokinetics and Interactions
The pharmacokinetics and interaction potentials of lipophilic statins, such as simvastatin, lovastatin, and fluvastatin, are different from those of hydrophilic statins 8. Strong inhibitors of CYP3A can greatly increase plasma concentrations of simvastatin, lovastatin, and their active acid forms, enhancing the risk of myotoxicity 8. Inhibitors of OATP1B1 may decrease the benefit-risk ratio of simvastatin, lovastatin, and pravastatin by interfering with their entry into hepatocytes 8, 9.