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PharmGKB · ClinPGx

Lovastatin Pathway, Pharmacokinetics

PA166254441 Last updated February 2022 Caroline F. Thorn & Li Gong
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Drugs & chemicals
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Conditions
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Reactions
Lovastatin Pathway, Pharmacokinetics pathway diagram
Lovastatin Pathway, Pharmacokinetics — pathway diagram from PharmGKB / ClinPGx
Click to enlarge

About this pathway

Background

Lovastatin is an HMG-CoA reductase inhibitor (statin) used for the lower cholesterol. Similar to other statins, pravastatin inhibits endogenous cholesterol production by competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the enzyme that catalyzes conversion of HMG-CoA to mevalonate depicted in the Statin Pathway, Pharmacodynamics.

Guideline regarding the use of pharmacogenomic information in dosing for lovastatin was published by the Clinical Pharmacogenetic Implementation Consortium (CPIC). CPIC recommends alternative statin for patients with SLCO1B1 rs4149056 (521T>C) CC or TC genotype, or patients with SLCO1B1 decreased function, or poor function phenotype.

Metabolism

Lovastatin is administered as an inactive lactone, and hydrolyzed in vivo to the corresponding β hydroxyacid form, a strong inhibitor of HMG-CoA reductase. The extensive first pass metabolism in the liver is mediated by CYP3A4 and CYP3A5 [Articles:17178259, 10490896, 20386561, 7905377, 2297361].

Transport

Lovastatin is a substrate of organic anion transporter SLCO1B1 and efflux transporter ABCB1 [Article:17178259]. Genetic variations in the SLCO1B1 gene have been linked to increased exposure of lovastatin acid. Carriers of the rs4149056 (521T>C) C allele had markedly increased AUC of lovastatin acid [Articles:27967318, 26020121], but have no significant effect on lovastatin lactone. rs4149056 C allele is also associated with an increased risk of statin-induced myopathy and rhabdomyolysis [Article:34114646].

Reactions & interactions (11)

  • Biochemical Reaction
    lovastatin → 6'-exomethylene lovastatin
  • Biochemical Reaction
    lovastatin → 6'beta-hydroxylovastatin
  • Biochemical Reaction
    lovastatin → 3"-hydroxy lovastatin
  • Catalysis
    CYP3A4 → Biochemical Reaction
  • Catalysis
    CYP3A4 → Biochemical Reaction
  • Catalysis
    CYP3A5 → Biochemical Reaction
  • Catalysis
    SLCO1B1 → Transport
  • Catalysis
    CYP3A4 → Biochemical Reaction
  • Catalysis
    ABCB1 → Transport
  • Transport
    lovastatin → lovastatin
  • Transport
    lovastatin → lovastatin

Edit history (3)

  • 2021-11-04 Create
  • 2022-02-20 Update Pathway updated to be specific for lovastatin and its metabolites, new gpml, new figure and text.
  • 2022-02-20 Update Linked related statin pathways.
Lovastatin Pathway, Pharmacokinetics pathway diagram (enlarged)