Drug Metabolism & Transporters

Phase I Metabolism

TRFaz I Metabolizma
Also known as:Phase 1 metabolism · Functionalization reactions

Functionalization reactions, mainly oxidation, reduction and hydrolysis, that introduce or unmask a polar group such as –OH, –NH2 or –COOH on a drug molecule.

In depth

Oxidation by cytochrome P450 enzymes dominates phase I metabolism; other oxidative enzymes include flavin-containing monooxygenases (FMOs), monoamine oxidases, alcohol and aldehyde dehydrogenases, and xanthine oxidase. Hydrolysis is catalyzed by esterases and amidases, and reduction by enzymes such as azo- and nitroreductases.

Phase I products may be inactive, retain activity, be more active (as in prodrug activation) or be reactive and toxic, as with N-acetyl-p-benzoquinone imine (NAPQI) formed from paracetamol. Many phase I metabolites subsequently undergo phase II conjugation.

Clinical pearl

Oxidative phase I capacity declines more with age and liver disease than glucuronidation does, which is why lorazepam or oxazepam is often preferred over diazepam in older adults and in cirrhosis.

Example drugs

Diazepam Codeine Enalapril paracetamol
TRIn Turkish

Faz I Metabolizma

İlaç molekülüne –OH, –NH2 veya –COOH gibi polar bir grup ekleyen ya da mevcut bir polar grubu açığa çıkaran, başlıca oksidasyon, redüksiyon ve hidroliz tepkimelerinden oluşan fonksiyonelleştirme reaksiyonlarıdır.

Faz I metabolizmada baskın tepkime sitokrom P450 enzimlerinin katalizlediği oksidasyondur; diğer oksidatif enzimler arasında flavin içeren monooksijenazlar (FMO), monoamin oksidazlar, alkol ve aldehit dehidrojenazlar ile ksantin oksidaz bulunur. Hidroliz esterazlar ve amidazlar, redüksiyon ise azo ve nitro redüktazlar gibi enzimler tarafından katalizlenir.

Faz I ürünleri inaktif olabilir, aktivitesini koruyabilir, daha aktif olabilir (ön ilaç aktivasyonunda olduğu gibi) ya da parasetamolden oluşan N-asetil-p-benzokinon imin (NAPQI) örneğindeki gibi reaktif ve toksik olabilir. Faz I metabolitlerinin çoğu ardından faz II konjugasyonuna uğrar.

Oksidatif faz I kapasitesi yaşlılıkta ve karaciğer hastalığında glukuronidasyona göre daha fazla azalır; bu nedenle yaşlılarda ve sirozda diazepam yerine sıklıkla lorazepam veya oksazepam tercih edilir.

Diğer adları:Faz 1 reaksiyonları · Fonksiyonelleştirme reaksiyonları
Updated 24.09.2026 1 views Educational reference — verify against current sources before clinical use.

Read next

Drug Metabolismİlaç Metabolizması

The enzymatic biotransformation of drugs and other xenobiotics into metabolites that are usually more polar and more readily excreted, occurring mainly in the liver.

 Phase II MetabolismFaz II Metabolizma

Conjugation reactions in which an endogenous moiety such as glucuronic acid, sulfate, glutathione, an acetyl or a methyl group is attached to a drug or to its phase I metabolite.

 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.

 ProdrugÖn İlaç (Prodrug)

A pharmacologically inactive or weakly active compound that is converted in the body, enzymatically or chemically, into the active drug.

 Active MetaboliteAktif Metabolit

A product of drug metabolism that has pharmacological activity of its own, which may be similar to, greater than or different from that of the parent drug.

 XenobioticKsenobiyotik

A chemical that is foreign to an organism, being neither produced by it nor part of its normal biochemistry; drugs, environmental pollutants, food additives and many plant toxins are examples.