Insights into CYP2B6-mediated drug–drug interactions
| Autor: | Hazem E. Hassan, William D. Hedrich, Hongbing Wang |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
CYP2B6 Review E2 estradiol Pharmacology 030226 pharmacology & pharmacy CPA cyclophosphamide C/EBP CCAAT/enhancer-binding protein chemistry.chemical_compound 0302 clinical medicine DDI drug–drug interaction RIF rifampin TCPOBOP 1 4-bis[3 5-dichloropyridyloxy]benzene Drug–drug interaction EFV efavirenz Constitutive androstane receptor ERE estrogen responsive element MAOI monoamine oxidase inhibitor General Pharmacology Toxicology and Pharmaceutics media_common Pregnane X receptor NVP nevirapine CITCO (6-(4-chlorophenyl)imidazo[2 1-b][1 3]thiazole-5-carbaldehyde-O-(3 4-dichlorobenzyl)oxime) PXR pregnane X receptor PCN pregnenolone 16 alpha-carbonitrile NR1/2 nuclear receptor binding site 1/2 PBREM phenobarbital-responsive enhancer module SNP single nucleotide polymorphism CAR CYP cytochrome P450 UGT UDP-glucuronosyl transferase CAR constitutive androstane receptor HNF hepatocyte nuclear factor Drug COUP-TF chicken ovalbumin upstream promoter-transcription factor PXR media_common.quotation_subject DEX dexamethasone Biology NNRTI non-nucleotide reverse-transcriptase inhibitor CHOP cyclophosphamide–doxorubicin–vincristine–prednisone 03 medical and health sciences CYP2B6 Gene Polymorphism Cyclophosphamide GR glucocorticoid receptor GRE glucocorticoid responsive element CYP3A4 lcsh:RM1-950 HAART highly active antiretroviral therapy IFA Ifosfamide lcsh:Therapeutics. Pharmacology 030104 developmental biology chemistry PB phenobarbital 4-OH-CPA 4-hydroxycyclophosphamide Efavirenz Xenobiotic Drug metabolism |
| Zdroj: | Acta Pharmaceutica Sinica. B Acta Pharmaceutica Sinica B, Vol 6, Iss 5, Pp 413-425 (2016) |
| ISSN: | 2211-3835 |
| DOI: | 10.1016/j.apsb.2016.07.016 |
| Popis: | Mounting evidence demonstrates that CYP2B6 plays a much larger role in human drug metabolism than was previously believed. The discovery of multiple important substrates of CYP2B6 as well as polymorphic differences has sparked increasing interest in the genetic and xenobiotic factors contributing to the expression and function of the enzyme. The expression of CYP2B6 is regulated primarily by the xenobiotic receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR) in the liver. In addition to CYP2B6, these receptors also mediate the inductive expression of CYP3A4, and a number of important phase II enzymes and drug transporters. CYP2B6 has been demonstrated to play a role in the metabolism of 2%–10% of clinically used drugs including widely used antineoplastic agents cyclophosphamide and ifosfamide, anesthetics propofol and ketamine, synthetic opioids pethidine and methadone, and the antiretrovirals nevirapine and efavirenz, among others. Significant inter-individual variability in the expression and function of the human CYP2B6 gene exists and can result in altered clinical outcomes in patients receiving treatment with CYP2B6-substrate drugs. These variances arise from a number of sources including genetic polymorphism, and xenobiotic intervention. In this review, we will provide an overview of the key players in CYP2B6 expression and function and highlight recent advances made in assessing clinical ramifications of important CYP2B6-mediated drug–drug interactions. Graphical abstract CYP2B6 is a highly inducible and polymorphic enzyme which plays a significant role in human drug metabolism. Variations in the expression and function of CYP2B6 significantly alter the metabolism and pharmacokinetics of many drugs. These alterations may result in significant drug–drug interactions which may lead to improved therapy or toxicity. fx1 |
| Databáze: | OpenAIRE |
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