Atorvastatin

Category: pharmacological

Aliases: Lipitor

Pharmacological Mechanism

Competitively inhibits HMG-CoA reductase (cholesterol synthesis) — the rate-limiting enzyme of cholesterol biosynthesis. ldl receptor pcsk9 axis LDLR upregulation → 40–60% LDL reduction at high-intensity doses. Pleiotropic effects (plaque stabilisation, endothelial function, anti-inflammation) contribute to CV benefit beyond LDL alone. Long t½ → any-time-of-day dosing (vs simvastatin evening).

Half-Life (t½)

PO: 11.4h

Dosing Guidelines

PO: Typical 33.3 mg (Range: 10–80 mg)

Target Organ Systems

cardiovascular
digestive
immune-hematologic

Interactions

CoQ10 (caution): Statins inhibit mevalonate pathway → reduced endogenous CoQ10. CoQ10 supplementation for statin-induced myopathy has moderate evidence.
Colchicine (caution): Additive myopathy / rhabdomyolysis risk. [Graham 2004]
Ezetimibe (synergistic): Additive LDL reduction; many combination products (Vytorin = simvastatin + ezetimibe).
Fenofibrate (caution): Additive myopathy risk (dose-dependent; gemfibrozil greater than fenofibrate). [Graham 2004]

Pathways It Modulates

Atherosclerosis plaque pathology (inhibitor) — HMG-CoA reductase → LDL ↓ + plaque stabilization
Cholesterol synthesis (inhibitor) — HMG-CoA reductase
Hippo / YAP-TAZ signaling (inhibitor) — HMG-CoA reductase → ↓RhoA geranylgeranylation → YAP inactivation
Klotho / FGF23 phosphate axis (inhibitor) — FGF23 (modest; vascular calcification context)
LDL receptor + PCSK9 axis (activator) — SREBP-2 activation → LDL-R upregulation (statin class mechanism)
NAFLD / MASH (inhibitor) — CV co-risk treatment in MASH; appears safe + may improve hepatic outcomes
PPAR α / γ / δ nuclear receptor signaling (activator) — PPARα/γ (off-target via cholesterol-pool depletion + direct)
Ubiquinone (CoQ10) biosynthesis (inhibitor) — CoQ10 depletion via HMG-CoA reductase block (statin class effect)

Chemical Identifiers

PubChem CID: 60823
Formula: C33H35FN2O5
Molecular weight: 558.64 g/mol
InChIKey: XUKUURHRXDUEBC-KAYWLYCHSA-N
SMILES: CC(C)C1=C(C(=C(N1CC[C@H](C[C@H](CC(=O)O)O)O)C2=CC=C(C=C2)F)C3=CC=CC=C3)C(=O)NC4=CC=CC=C4