## Statin Metabolism and Hepatic Safety **Key Point:** Pravastatin is hydrophilic and undergoes minimal hepatic metabolism (only 18%), making it the safest statin in hepatic impairment. ### Metabolism Comparison Table | Statin | Lipophilicity | Hepatic Metabolism | Renal Excretion | Safety in Liver Disease | | --- | --- | --- | --- | --- | | Pravastatin | Hydrophilic | 18% (minimal) | 60% unchanged | **Safest** | | Rosuvastatin | Hydrophilic | Minimal | 90% renal | Safe | | Simvastatin | Lipophilic | 90%+ (extensive) | Minimal | Contraindicated | | Atorvastatin | Lipophilic | 70% (extensive) | Minimal | Avoid | | Lovastatin | Lipophilic | 95%+ (extensive) | Minimal | Contraindicated | **High-Yield:** Pravastatin and rosuvastatin are the only statins that rely primarily on renal excretion rather than hepatic metabolism. Pravastatin is preferred in clinical practice due to its long track record and lower cost. **Clinical Pearl:** Hydrophilic statins (pravastatin, rosuvastatin) do not require CYP3A4 metabolism, reducing drug–drug interactions. Lipophilic statins (simvastatin, atorvastatin, lovastatin) are extensively metabolized by CYP3A4 and are contraindicated in severe hepatic disease. **Mnemonic:** **PRRS** — **P**ravastatin and **R**osuvastatin are **R**enal and **S**afe (in liver disease).
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