[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Biochemistry](https://durgical.com/en/biochemistry/) › Cytochrome P450 3A4 (CYP3A4)

[Biochemistry](https://durgical.com/en/biochemistry/) · Enzyme

# Cytochrome P450 3A4 (CYP3A4)

The most abundant P450 enzyme in liver and gut; it transforms about half of all drugs and is the key to many interactions.

Updated 2026-11-01

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## Key facts

- It metabolises about 50 % of commonly used drugs: statins, calcium channel blockers, ciclosporin and tacrolimus, macrolides, benzodiazepines, opioids, antiretrovirals.
- It is in the liver and in the enterocyte: it limits oral bioavailability (first-pass metabolism).
- Inducers (rifampicin, carbamazepine, phenytoin, St John's wort) lower its substrates' levels; inhibitors (azoles, clarithromycin, ritonavir, grapefruit juice) raise them.
- Its active site is large and flexible: it accepts very different molecules, even two at once.

**EC number**
[1.14.14.1](https://www.enzyme-database.org/query.php?ec=1.14.14.1)

**Genes**
CYP3A4

**Structure (PDB)**
[3NXU](https://www.rcsb.org/structure/3NXU)

## Structure

- Endoplasmic reticulum membrane monooxygenase with haem; a wide active pocket above the haem iron.

## Regulation

- Induction by transcription through the nuclear receptor PXR (and CAR) when an inducer binds.
- Competitive or mechanism-based inhibition (irreversible inactivation, as with ritonavir and grapefruit).

## Inhibitors and toxins

- Ritonavir and cobicistat (pharmacokinetic boosters; ritonavir in the 3D structure)
- Ketoconazole, itraconazole
- Clarithromycin, erythromycin
- Grapefruit juice furanocoumarins (in the gut)

## Clinical notes

- Rhabdomyolysis from simvastatin taken with a strong CYP3A4 inhibitor (clarithromycin, azoles).
- Rifampicin can make hormonal contraceptives, antiretrovirals and immunosuppressants fail by inducing the enzyme.
- Ritonavir is used on purpose to inhibit it and raise the level of other antiretrovirals.
- Transplant rejection if an inducer lowers tacrolimus; kidney toxicity if an inhibitor raises it.

## Related conditions

- [HIV infection and AIDS](https://durgical.com/en/conditions/hiv-infection-and-aids/)
- [Tuberculosis](https://durgical.com/en/conditions/tuberculosis/)

## Related

- [Cytochrome P450 system](https://durgical.com/en/biochemistry/topics/cytochrome-p450-system/)
- [Xenobiotic biotransformation: phases I, II and III](https://durgical.com/en/biochemistry/topics/xenobiotic-biotransformation-phases-i-ii-and-iii/)
- [Cytochrome P450 2E1 (CYP2E1, MEOS)](https://durgical.com/en/biochemistry/enzymes/cytochrome-p450-2e1/)
- [Heme](https://durgical.com/en/biochemistry/molecules/heme/)
- [NADPH](https://durgical.com/en/biochemistry/molecules/nadph/)
- [HMG-CoA reductase](https://durgical.com/en/biochemistry/enzymes/hmg-coa-reductase/)

## Test yourself

Think of the answer, then tap the question to see it.

## What happens to a statin such as simvastatin combined with clarithromycin?

Clarithromycin inhibits CYP3A4, the statin level rises and the risk of myopathy and rhabdomyolysis increases.

## Why does rifampicin weaken many drugs?

It activates the PXR receptor, which induces CYP3A4 synthesis, so the drugs are cleared faster.

## Why is ritonavir combined with other antiretrovirals?

To inhibit CYP3A4 and raise their levels: it is a pharmacokinetic booster.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [CYP3A4: Cytochrome P450 3A4 (human), UniProt P08684](https://www.uniprot.org/uniprotkb/P08684/entry) (UniProt, 2026); [RCSB PDB - 3NXU: Crystal structure of human cytochrome P4503A4 bound to an inhibitor ritonavir](https://www.rcsb.org/structure/3NXU) (RCSB Protein Data Bank, 2026); [Cytochrome P450 - arranged by substrate type](https://reactome.org/PathwayBrowser/#/R-HSA-211897) (Reactome, 2026); [What is pharmacogenomics?: MedlinePlus Genetics](https://medlineplus.gov/genetics/understanding/genomicresearch/pharmacogenomics/) (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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