title: HMG-CoA reductase inhibitors: assessing differences in drug interactions and safety profiles.
abstract: OBJECTIVE
  To review the cytochrome P450 system and associated metabolic differences between the HMG-CoA reductase inhibitors.
  
  
  METHODS
  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.
  
  
  METHODS
  Review articles, clinical trials, and case reports concerning HMG-CoA reductase inhibitor metabolism, drug interactions, and adverse drug reactions were evaluated.
  
  
  METHODS
  By the author. No software or assistants were used to extract information from the chosen studies.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: HealthTech Solutions, St. Louis, MO 63146, USA. sbeaird@htsmail.com
authors.forename: S L
authors.initials: SL
authors.lastname: Beaird
mesh_terms: D002800:Cholinesterase Inhibitors / Q000009:adverse effects*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*
chemical_list: D002800:Cholinesterase Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D003577:Cytochrome P-450 Enzyme System