HMG-CoA reductase inhibitors: assessing differences in drug interactions and safety profiles

J Am Pharm Assoc (Wash). Sep-Oct 2000;40(5):637-44. doi: 10.1016/s1086-5802(16)31104-4.


Objective: To review the cytochrome P450 system and associated metabolic differences between the HMG-CoA reductase inhibitors.

Data sources: A MEDLINE search (1993-99) was conducted for English-language articles using key search terms including adverse drug reactions, cytochrome P450, drug metabolism, drug interactions, hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors, myopathy, and rhabdomyolysis.

Study selection: Review articles, clinical trials, and case reports concerning HMG-CoA reductase inhibitor metabolism, drug interactions, and adverse drug reactions were evaluated.

Data extraction: By the author. No software or assistants were used to extract information from the chosen studies.

Data synthesis: The cytochrome P450 enzymes, which can be divided into families, subfamilies, and isoenzymes, act as a major catalyst for drug oxidation in the liver. CYP3A4 is a major enzyme, accounting for about 60% of drug metabolic capacity in the liver and 70% of such function in the intestine. Lovastatin, simvastatin, and atorvastatin are substrates of CYP3A4, whereas fluvastatin is metabolized by CYP2C9. Pravastatin is not extensively metabolized by either of these isoenzymes; rather, it is transported into hepatocytes by a sodium-independent, carrier-mediated uptake system that normally transports bile acids. Compared with other statins, pravastatin thus has a reduced potential for drug interactions with other substrates, inhibitors, or inducers of the CYP3A4 and CYP2C9 systems.

Conclusion: Pharmacists must understand the functions of these enzymes to identify potential drug interactions, especially in high-risk patient populations, and to make appropriate therapeutic recommendations that prevent or minimize adverse clinical outcomes.

Publication types

  • Review

MeSH terms

  • Cholinesterase Inhibitors / adverse effects*
  • Cytochrome P-450 Enzyme System / metabolism
  • Drug Interactions
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*


  • Cholinesterase Inhibitors
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Cytochrome P-450 Enzyme System