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