What are UGT1A1 inhibitors?
A purine base which forms a component of DNA among other functions and is present in many multivitamins. A medication used in general anesthesia and for sedation.
What drugs are UGT inhibitors?
Figure 1
| UGT Isoform | Substrate | Inhibitor |
|---|---|---|
| UGT1A3 | Sulindac sulfone | Ritonavir Quinidine |
| UGT1A4 | Trifluoperazine | Diclofenac |
| UGT1A6 | Naphthol | Diclofenac |
| UGT1A9 | Propofol | Diclofenac Mycophenolic acid |
What are CYP2C19 inhibitors?
CYP2C19 catalyzes the metabolism of several drugs, including proton pump inhibitors (PPIs) (e.g., omeprazole, lansoprazole, pantoprazole), antidepressants (e.g., citalopram and amitriptyline), antiplatelet drugs (e.g., clopidogrel), antifungals (e.g., voriconazole), and anticancer compounds (e.g., cyclophosphamide).
What drugs are metabolized by UGT1A1?
Many exogenous substances, mutagenic xenobiotics and therapeutic drugs are UGT1A1 substrates. Examples of therapeutic drug substrates of UGT1A1 are: irinotecan (SN-38), acetaminophen (paracetamol), carvedilol, etoposide, lamotrigine and simvastatin [1-3].
What is a CYP3A4 inhibitor?
CYP3A4 is responsible for the metabolism of more than 50% of medicines. Potent inhibitors of CYP3A4 include clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, goldenseal and grapefruit. Inducers of CYP3A4 include phenobarbital, phenytoin, rifampicin, St.
What is irinotecan based chemotherapy?
Irinotecan is a type of chemotherapy. It is also known by its brand name Campto. It is a treatment for cancer that started in the bowel (bowel cancer). This includes the colon and back passage (rectum).
Where is UGT enzyme located?
the liver
The bilirubin-UGT enzyme is primarily found in cells of the liver, where bilirubin glucuronidation takes place. Conjugated bilirubin is dissolved in bile, a fluid produced in the liver, and excreted with solid waste.
What are UGT inducers?
If a drug is an inducer (perpetrator) of a CYP enzyme that is responsible for its own metabolism or the metabolism of another drug (victim), then concomitant administration of the perpetrator and victim can mean faster clearance of the victim drug. …
What is the CYP2C19 gene?
The CYP2C19 gene is a member of the cytochrome P450 gene family. The CYP2C19 gene provides instructions for making an enzyme that is found primarily in liver cells in a cell structure called the endoplasmic reticulum, which is involved in protein processing and transport.
What is CYP2C19 phenotype?
The CYP2C19 “poor metabolism” phenotype was initially discovered by studies on impaired mephenytoin metabolism and the major molecular defect responsible for the trait is the CYP2C19*2 (c. 681G>A; rs4244285) loss-of-function allele [Article:8195181].
What is UGT1A1 gene?
The UGT1A1 gene belongs to a family of genes that provide instructions for making enzymes called UDP-glucuronosyltransferases. These enzymes perform a chemical reaction called glucuronidation, in which a compound called glucuronic acid is attached (conjugated) to one of a number of different substances.
Is amiodarone a CYP3A4 inhibitor?
Amiodarone is a substrate of CYP3A4 and CYP2C8 and an inhibitor of CYP2C9, CYP2D6, CYP3A4, and p-glycoprotein.
What is the role of UGT1A9 in the liver?
UGT1A9 is the major isoform responsible for the glucuronidations of fraxetin in liver microsomes. In HeLa cells overexpressing UGT1A9 there was an increase in catalysis and production of luteolin glucuronides.
Which is the substrate specificity of UGT1A9?
Data suggest that the substrate specificity of UGT1A9 includes the antiviral drug arbidol; UGT1A9 appears to be the major UGT isoform involved in the formation of arbidol glucuronides by liver microsomes. UGT1A9 and 2B7 are the main enzymes involved in ethanol glucuronidation.
Are there any mutations in the UGT1A9 gene?
None of the patients with Regorafenib-induced severe toxic hepatitis had CYP3A4 gene mutations. Similar polymorphisms in UGT1A9 gene promoter region were found in both patients who presented acute hepatitis.
How does UGT1A9 affect mycophenolic acid metabolism?
The effect of UGT1A8 and UGT1A9 variants on mycophenolic acid metabolism appears to be modified by concomitant calcineurin inhibitor therapy.