What are hydrophilic statins (3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors)?

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Last updated: April 15, 2025View editorial policy

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From the Guidelines

Hydrophilic statins, which include rosuvastatin and pravastatin, are the recommended options for patients who require a water-soluble statin with less penetration into non-hepatic tissues, potentially resulting in fewer muscle-related side effects. These medications are cholesterol-lowering drugs that differ from lipophilic statins in their chemical properties and tissue distribution 1. Hydrophilic statins are particularly useful for patients who have experienced muscle pain or weakness with other statins.

Key Characteristics of Hydrophilic Statins

  • Water-soluble
  • Less penetration into non-hepatic tissues
  • Liver-selective property through active transport mechanisms
  • Potential for fewer muscle-related side effects

Examples of Hydrophilic Statins

  • Rosuvastatin (Crestor)
  • Pravastatin (Pravachol)

Typical Dosing

  • Rosuvastatin: 5-40 mg daily
  • Pravastatin: 10-80 mg daily It is essential to note that these medications are most effective when taken with lifestyle modifications, including diet changes and exercise 1. Patients with kidney disease may require dose adjustments of rosuvastatin as it is partially eliminated through renal pathways. The use of hydrophilic statins should be guided by the most recent clinical guidelines and patient-specific factors, such as history of muscle-related side effects and kidney function.

From the FDA Drug Label

Rosuvastatin calcium is a hydrophilic compound with a partition coefficient (octanol/water) of 1.4 at pH of 7.0. Pravastatin sodium, USP is a relatively polar hydrophilic compound with a partition coefficient (octanol/water) of 0.59 at a pH of 7. 0.

Hydrophilic statins are:

  • Rosuvastatin 2
  • Pravastatin 3

From the Research

Hydrophilic Statins

  • Hydrophilic statins are a type of statin that presents greater hepatoselectivity, meaning they are more selective to the liver and less likely to enter other cells 4.
  • The hydrophilic statins include:
    • Rosuvastatin
    • Pravastatin
  • These statins are less likely to cause muscle toxicity compared to lipophilic statins, as they are less likely to enter muscle cells 5.
  • Hydrophilic statins, such as pravastatin, have been shown to lower blood total cholesterol, LDL cholesterol, and triglyceride in a dose-dependent linear fashion 6.

Comparison with Lipophilic Statins

  • Lipophilic statins, such as simvastatin, fluvastatin, pitavastatin, lovastatin, and atorvastatin, can easily enter cells and may be more effective at lowering LDL cholesterol, but may also be more likely to cause muscle toxicity 4, 5.
  • Pitavastatin, a lipophilic statin, has been shown to be effective in lowering LDL-C levels and is generally well tolerated, but may not be as hepatoselective as hydrophilic statins like pravastatin and rosuvastatin 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Hydrophilic or Lipophilic Statins?

Frontiers in cardiovascular medicine, 2021

Research

Pravastatin for lowering lipids.

The Cochrane database of systematic reviews, 2023

Research

Pitavastatin: A Review in Hypercholesterolemia.

American journal of cardiovascular drugs : drugs, devices, and other interventions, 2017

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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