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Simvastatin

Indications
  • hypercholesterolemia
  • Effective in reducing total and LDL-cholesterol as well as plasma triglycerides and apolipoprotein B
Dosage
  • 5 - 80 mg per day
Administration/Absorption
  • Oral
    • 85% absorption
Distribution
  • Both simvastatin and its b-hydroxyacid metabolite are highly bound (approximately 95%) to human plasma proteins
Mechanism
  • Potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl COA reductases)
    • The 6-membered lactone ring of simvastatin is hydrolyzed in vivo to generate the beta,delta-dihydroxy acid
      • An active metabolite structurally similar to HMG-CoA (hydroxymethylglutaryl CoA)
    • Once hydrolyzed, simvastatin competes with HMG-CoA for HMG-CoA reductase, a hepatic microsomal enzyme
    • Interference with the activity of this enzyme reduces the quantity of mevalonic acid, a precursor of cholesterol
  • May also interfere with steroid hormone production
  • Due to the induction of hepatic LDL receptors, it increases breakdown of LDL cholesterol
Excretion
  • Half-life 3 hours
  • Following an oral dose of 14C-labeled simvastatin in man, 13% of the dose was excreted in urine and 60% in feces
Side effects
  • Common side effects (>1% incidence) may include abdominal pain, diarrhea, indigestion, and a general feeling of weakness
  • Rare side effects include joint pain, memory loss, and muscle cramps.[2]
  • Cholestatic hepatitis, hepatic cirrhosis, rhabdomyolysis and myositis have been reported in patients receiving the drug chronically
Interactions
Contraindications

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