[Metabolic interactions with statins].
BACKGROUND
Isoenzymes of the cytochrome P450 (CYP) system play a prominent role in drug metabolism, including the HMG-CoA reductase inhibitors (statins). Alteration in metabolic activity is often the underlying mechanism of clinically relevant interactions, thus it is important to make a rational assessment of the risk for metabolic interactions with statins.


METHODS
Articles covering the field of statin metabolism and related interactions were mainly searched for via PubMed.


RESULTS
More than 50% of the overall CYP metabolism is mediated through the isoenzyme CYP3A4, which is the main elimination route of simvastatin, lovastatin and atorvastatin. Interaction studies reveal that simvastatin and lovastatin have the highest potential for clinically relevant interactions related to this isoenzyme, most often leading to increased efficacy/toxicity of the statin. Interactions with agents that alter the activity of CYP3A4 can also be expected for atorvastatin. Other statins are to a lesser extent dependent on CYP3A4 in their elimination. Thus, pravastatin, cerivastatin and fluvastatin have a minor potential for interactions linked to this isoenzyme. Interactions associated with CYP2C9-interference may, however, be present for fluvastatin.


CONCLUSIONS
Since lipid-lowering therapy most often is life-long, the use of statins will frequently be accompanied by the use of multiple drugs, hence the importance of considering the risk for interactions when selecting statins.
Molden
E
E
Avdeling for farmakologi Farmasøytisk institutt Universitetet i Oslo Postboks 1068 Blindern 0316 Oslo. espen.molden@farmasi.uio.no
Asberg
A
A
D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000378:metabolism; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000378:metabolism*; D000925:Anticoagulants / Q000009:adverse effects / Q000378:metabolism; D001393:Azoles / Q000009:adverse effects / Q000378:metabolism; D001628:Beverages / Q000009:adverse effects; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000378:metabolism; D002957:Citrus; D016572:Cyclosporine / Q000009:adverse effects / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000378:metabolism; D018942:Macrolides; D012307:Risk Factors; D014859:Warfarin / Q000009:adverse effects / Q000378:metabolism
D000900:Anti-Bacterial Agents; D000924:Anticholesteremic Agents; D000925:Anticoagulants; D001393:Azoles; D002121:Calcium Channel Blockers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D018942:Macrolides; D014859:Warfarin; D016572:Cyclosporine; D003577:Cytochrome P-450 Enzyme System