Simvastatin

Category: pharmacological

Aliases: Zocor

Pharmacological Mechanism

Lactone prodrug of simvastatin acid. Lipophilic — greater CNS penetration than rosuvastatin. CYP3A4 substrate — heavy interaction profile. Peak endogenous cholesterol synthesis occurs nocturnally → evening dosing for short-t½ statins.

Half-Life (t½)

PO: 3h

Dosing Guidelines

• PO: Typical 16.7 mg (Range: 5–40 mg)

Target Organ Systems

• cardiovascular
• digestive

Interactions

• Gemfibrozil (major): CYP2C8 inhibition raises statin levels — FDA explicit warning. Avoid. [Graham 2004]

Pathways It Modulates

• Atherosclerosis plaque pathology (inhibitor) — HMG-CoA reductase
• Cholesterol synthesis (inhibitor) — HMG-CoA reductase
• Hippo / YAP-TAZ signaling (inhibitor) — HMG-CoA reductase → YAP suppression (cancer chemoprevention partial mechanism)
• PPAR α / γ / δ nuclear receptor signaling (activator) — PPARα/γ (off-target)

Chemical Identifiers

• PubChem CID: 54454
• Formula: C25H38O5
• Molecular weight: 418.57 g/mol
• InChIKey: RYMZZMVNJRMUDD-HGQWONQESA-N
• SMILES: CCC(C)(C)C(=O)O[C@H]1C[C@H](C=C2[C@H]1[C@H]([C@H](C=C2)C)CC[C@@H]3C[C@H](CC(=O)O3)O)C

References

• PMID 8343198