Drug Metabolism & Transporters

Glucuronidation

TRGlukuronidasyon
Also known as:Glucuronide conjugation · Glucuronic acid conjugation

A phase II conjugation reaction in which UDP-glucuronosyltransferases (UGTs) transfer glucuronic acid from UDP-glucuronic acid to a hydroxyl, carboxyl, amine or thiol group on a drug or metabolite.

In depth

Glucuronidation is quantitatively the most important phase II pathway. UGTs are membrane-bound enzymes of the endoplasmic reticulum expressed in liver, intestine and kidney; major drug-metabolizing isoforms include UGT1A1, UGT1A4, UGT1A9 and UGT2B7. Glucuronides are generally inactive and water-soluble and are excreted in urine or bile, where bacterial β-glucuronidase can release the parent drug for enterohepatic recirculation.

Exceptions include the active morphine-6-glucuronide and the reactive acyl glucuronides of some carboxylic acid drugs. UGT1A1 also conjugates bilirubin; reduced-function variants (UGT1A1*28, *6) underlie Gilbert syndrome and increase irinotecan toxicity.

Clinical pearl

Valproate inhibits lamotrigine glucuronidation, roughly doubling its half-life; lamotrigine is therefore started and titrated at reduced doses alongside valproate to limit the risk of serious rash.

Example drugs

Morphine Lorazepam Lamotrigine Irinotecan Zidovudine
TRIn Turkish

Glukuronidasyon

UDP-glukuronoziltransferazların (UGT'ler) glukuronik asidi UDP-glukuronik asitten bir ilacın veya metabolitin hidroksil, karboksil, amin ya da tiyol grubuna aktardığı faz II konjugasyon tepkimesidir.

Glukuronidasyon nicel olarak en önemli faz II yoludur. UGT'ler karaciğer, bağırsak ve böbrekte eksprese edilen, endoplazmik retikuluma bağlı membran enzimleridir; ilaç metabolizmasında başlıca izoformlar UGT1A1, UGT1A4, UGT1A9 ve UGT2B7'dir. Glukuronidler genellikle inaktif ve suda çözünürdür; idrar veya safra ile atılır. Safradaki glukuronidlerden bağırsak bakterilerinin β-glukuronidazı ana ilacı serbestleştirerek enterohepatik dolaşıma katılmasını sağlayabilir.

İstisnalar arasında aktif morfin-6-glukuronid ve bazı karboksilik asit yapılı ilaçların reaktif açil glukuronidleri bulunur. UGT1A1 bilirubini de konjuge eder; işlevi azalmış varyantlar (UGT1A1*28, *6) Gilbert sendromunun temelini oluşturur ve irinotekan toksisitesini artırır.

Valproat lamotrijinin glukuronidasyonunu inhibe ederek yarılanma ömrünü yaklaşık iki katına çıkarır; bu nedenle ciddi döküntü riskini sınırlamak için valproatla birlikte lamotrijine daha düşük dozlarla başlanır ve titrasyon daha yavaş yapılır.

Diğer adları:Glukuronid konjugasyonu · Glukuronik asit konjugasyonu
Updated 24.09.2026 0 views Educational reference — verify against current sources before clinical use.

Read next

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.

 Enterohepatic RecirculationEnterohepatik Dolaşım

The cycle in which a drug or its conjugated metabolite is excreted in bile into the intestine, reabsorbed (after deconjugation, if conjugated) and returned to the liver via the portal circulation.

 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.

 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.

 PharmacogenomicsFarmakogenomik

The study of how inherited genetic variation affects an individual's response to drugs, used clinically to guide drug and dose selection.

 ExcretionAtılım (Ekskresyon)

The removal of unchanged drug or its metabolites from the body, principally in urine and in bile (faeces), and to a lesser extent in exhaled air, sweat, saliva and breast milk.