CYP3A4/3A5 Substrates

    CYP3A4/3A5 substrates include, but are not limited to, tacrolimus, and some benzodiazepines (e.g., alprazolam, diazepam, midazolam), statin medications (e.g., atorvastatin, lovastatin, simvastatin), and calcium-channel blockers (e..g, felodipine, nifedipine, diltiazem, verapamil). See glossary page for more information.

    Summary

    CYP3A4/3A5 substrates are compounds that are metabolized by CYP3A4 and CPY3A5 (cytochrome P450 enzymes), but do not necessarily affect their activity.

    CYP3A4 and CYP3A5 are structurally very similar and largely share the same substrates, but CYP3A5 is generally considered to be less metabolically active and is usually present in lower amounts, particularly in people of European descent.[1]

    In the presence of CYP3A4/3A5 inhibitors or inducers, the metabolism of CYP3A4/3A5 substrates can be affected.

    The table below outlines some of the most common or clinically relevant CYP3A4/3A5 substrates.[1][2][3] Importantly, this list is not exhaustive.

    CYP3A4/3A5 Substrates
    Acetaminophen
    Alprazolam
    Aprepitant
    Atorvastatin
    Budesonide
    Buprenorphine
    Carbamazepine
    Citalopram
    Clarithromycin
    Clindamycin
    Codeine
    Colchicine
    Cyclobenzaprine
    Cyclophosphamide*
    Cyclosporine
    Dexamethasone
    Dextromethorphan
    Diazepam
    Diltiazem
    Docetaxel
    Eletriptan
    Felodipine
    Fenofibrate
    Fentanyl
    Glyburide
    Haloperidol
    Hydromorphone
    Indinavir
    Irinotecan
    Isotretinoin
    Loperamide
    Lopinavir
    Lovastatin
    Methadone
    Midazolam
    Mifepristone
    Mirtazapine
    Nifedipine
    Oxycodone
    Quetiapine
    Quinine
    Ritonavir
    Rivaroxaban
    Sildenafil
    Simvastatin
    Tacrolimus
    Tadalafil
    Testosterone
    Ticagrelor
    Tramadol
    Trazodone
    Triazolam
    Verapamil
    Zolpidem

    * Prodrugs are indicated with an asterisk

    References

    1. ^Song Y, Li C, Liu G, Liu R, Chen Y, Li W, Cao Z, Zhao B, Lu C, Liu YDrug-Metabolizing Cytochrome P450 Enzymes Have Multifarious Influences on Treatment Outcomes.Clin Pharmacokinet.(2021-May)
    2. ^Zanger UM, Schwab MCytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation.Pharmacol Ther.(2013-Apr)
    3. ^Hakkola J, Hukkanen J, Turpeinen M, Pelkonen OInhibition and induction of CYP enzymes in humans: an update.Arch Toxicol.(2020-Nov)