Drug Metabolism & Transporters

CYP3A4

Also known as:Cytochrome P450 3A4

The most abundant cytochrome P450 isoform in the human liver and small-intestinal epithelium, responsible for the oxidative metabolism of a large proportion of clinically used drugs.

In depth

CYP3A4 has a large, flexible active site and a very broad substrate range, including many benzodiazepines, calcium-channel blockers, calcineurin inhibitors, several statins (simvastatin, lovastatin, atorvastatin), macrolides, azole antifungals, HIV protease inhibitors and kinase inhibitors. Its expression in enterocytes, together with P-glycoprotein, makes it a major determinant of oral bioavailability and first-pass metabolism.

Strong inhibitors include ketoconazole, itraconazole, clarithromycin, ritonavir and cobicistat; grapefruit juice inhibits mainly the intestinal enzyme. Strong inducers include rifampicin, carbamazepine, phenytoin and St. John's wort. Activity varies considerably between individuals, and CYP3A5 shares many of its substrates.

Clinical pearl

Combining simvastatin or lovastatin with a strong CYP3A4 inhibitor (e.g. clarithromycin, itraconazole, ritonavir) markedly raises statin exposure and the risk of myopathy and rhabdomyolysis, and is contraindicated.

Example drugs

Midazolam Simvastatin Tacrolimus ciclosporin Nifedipine
TRIn Turkish

CYP3A4

İnsan karaciğerinde ve ince bağırsak epitelinde en bol bulunan sitokrom P450 izoformudur; klinikte kullanılan ilaçların önemli bir bölümünün oksidatif metabolizmasından sorumludur.

CYP3A4'ün büyük ve esnek bir aktif bölgesi ve çok geniş bir substrat yelpazesi vardır; birçok benzodiazepin, kalsiyum kanal blokeri, kalsinörin inhibitörü, bazı statinler (simvastatin, lovastatin, atorvastatin), makrolidler, azol antifungaller, HIV proteaz inhibitörleri ve kinaz inhibitörleri bu enzimin substratıdır. Enterositlerde P-glikoproteinle birlikte eksprese edilmesi, onu oral biyoyararlanımın ve ilk geçiş metabolizmasının başlıca belirleyicilerinden biri yapar.

Güçlü inhibitörler arasında ketokonazol, itrakonazol, klaritromisin, ritonavir ve kobisistat yer alır; greyfurt suyu başlıca bağırsaktaki enzimi inhibe eder. Güçlü indükleyiciler arasında rifampisin, karbamazepin, fenitoin ve sarı kantaron bulunur. Aktivite bireyler arasında belirgin farklılık gösterir ve CYP3A5 substratlarının birçoğunu paylaşır.

Simvastatin veya lovastatinin güçlü bir CYP3A4 inhibitörüyle (ör. klaritromisin, itrakonazol, ritonavir) birlikte kullanımı statin maruziyetini ve miyopati ile rabdomiyoliz riskini belirgin şekilde artırır; bu kombinasyon kontrendikedir.

Diğer adları:Sitokrom P450 3A4
Updated 24.09.2026 0 views Educational reference — verify against current sources before clinical use.

Read next

Cytochrome P450Sitokrom P450

A superfamily of heme-containing monooxygenase enzymes, located mainly in the endoplasmic reticulum of hepatocytes and enterocytes, that catalyze most phase I oxidative drug metabolism.

 P-glycoproteinP-glikoprotein

An ATP-dependent efflux transporter (ABCB1, MDR1) that pumps a wide range of drugs out of cells, limiting their intestinal absorption and brain entry and promoting their biliary and renal excretion.

 Grapefruit Juice InteractionGreyfurt Suyu Etkileşimi

An interaction in which furanocoumarins in grapefruit juice irreversibly inhibit intestinal CYP3A4, increasing the oral bioavailability of drugs that undergo extensive first-pass metabolism by this enzyme.

 Enzyme InhibitionEnzim İnhibisyonu

A reduction in the activity of a drug-metabolizing enzyme by a co-administered drug or other substance, which lowers the clearance of drugs dependent on that enzyme and raises their concentrations.

 Enzyme InductionEnzim İndüksiyonu

An increase in the amount and activity of a drug-metabolizing enzyme or transporter, usually through enhanced gene transcription, caused by repeated exposure to a drug or other xenobiotic.

 First-Pass Effectİlk Geçiş Etkisi

The metabolism of a drug in the liver (or gut wall) before it reaches systemic circulation, often reducing the bioavailability of orally administered drugs.