CYP2C9 - CYP2C9 Ligands

CYP2C9 Ligands

Most inhibitors of CYP2C9 are competitive inhibitors. Noncompetitive inhibitors of CYP2C9 include nifedipine, tranylcypromine, phenethyl isothiocyanate, medroxyprogesterone acetate and 6-hydroxyflavone. It was indicated that the noncompetitive binding site of 6-hydroxyflavone is the reported allosteric binding site of the CYP2C9 enzyme.

Following is a table of selected substrates, inducers and inhibitors of CYP2C9. Where classes of agents are listed, there may be exceptions within the class.

Inhibitors of CYP2C9 can be classified by their potency, such as:

  • Strong being one that causes at least a 5-fold increase in the plasma AUC values, or more than 80% decrease in clearance.
  • Moderate being one that causes at least a 2-fold increase in the plasma AUC values, or 50-80% decrease in clearance.
  • Weak being one that causes at least a 1.25-fold but less than 2-fold increase in the plasma AUC values, or 20-50% decrease in clearance.
Selected inducers, inhibitors and substrates of CYP2C9
Substrates Inhibitors Inducers
  • NSAIDs (analgesic, antipyretic, anti-inflammatory)
    • celecoxib
    • lornoxicam
    • diclofenac
    • ibuprofen
    • naproxen
    • piroxicam
    • meloxicam
    • suprofen
  • phenytoin (antiepileptic)
  • fluvastatin (statin)
  • sulfonylureas (antidiabetic)
    • glipizide
    • glibenclamide
    • glimepiride
    • tolbutamide
    • glyburide
  • angiotensin II receptor antagonists (in hypertension, diabetic nephropathy, CHF)
    • irbesartan
    • losartan
  • S-warfarin (anticoagulant)
  • sildenafil (in erectile dysfunction)
  • terbinafine (antifungal)
  • amitriptyline (tricyclic antidepressant)
  • fluoxetine (SSRI antidepressant)
  • nateglinide (antidiabetic)
  • rosiglitazone (antidiabetic)
  • tamoxifen (SERM)
  • torasemide (loop diuretic)
 Strong:
  • fluconazole (antifungal)
  • miconazole (antifungal)
  • amentoflavone (constituent of Ginkgo biloba and St. John’s Wort)
  • sulfaphenazole (antibacterial)
  • Valproic acid (anticonvulsant, mood-stabilizing)

Moderate

  • amiodarone (antiarrhythmic)

Unspecified potency

  • antihistamines (H1-receptor antagonists)
    • Cyclizine
    • Promethazine
  • Chloramphenicol
  • fenofibrate (fibrate)
  • flavones
  • flavonols
  • fluvastatin (statin)
  • fluvoxamine (SSRI)
  • isoniazid (in tuberculosis)
  • lovastatin (statin)
  • phenylbutazone (NSAID)
  • probenecid (uricosuric)
  • sertraline (SSRI)
  • sulfamethoxazole (antibiotic)
  • teniposide (chemotherapeutic)
  • voriconazole (antifungal)
  • zafirlukast (leukotriene antagonist)
  • quercetin (anti-inflammatory)
 Strong:
  • rifampicin (bactericidal)
  • secobarbital (barbiturate)

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