Inhibition of human hepatic cytochrome P4502E1 by azole antifungals, CNS-active drugs and non-steroidal anti-inflammatory agents.
Article Details
- CitationCopy to clipboard
Tassaneeyakul W, Birkett DJ, Miners JO
Inhibition of human hepatic cytochrome P4502E1 by azole antifungals, CNS-active drugs and non-steroidal anti-inflammatory agents.
Xenobiotica. 1998 Mar;28(3):293-301. doi: 10.1080/004982598239579 .
- PubMed ID
- 9574817 [ View in PubMed]
- Abstract
1. The capacity of a number of antifungal azoles, CNS-active drugs (anticonvulsants, antidepressants, antipsychotics and benzodiazepine hypnosedative-anxiolytics) and nonsteroidal anti-inflammatory agents (NSAIDs) to inhibit human liver microsomal 4-nitrophenol (4NP) hydroxylation, a marker of CYP2E1 activity, was investigated. 2. The imidazoles bifonazole, clotrimazole, econazole and miconazole were un- or non-competitive inhibitors of 4NP hydroxylation, with apparent Ki values ranging from 4 to 25 microM. Fluonazole, itraconazole and ketoconazole caused minor or negligible inhibition. 3. Of the CNS-active drugs screened, significant inhibition occurred only with tricyclic antidepressants, phenothiazine antipsychotics and two benzodiazepines (flurazepam and medazepam). Un- or non-competitive inhibition was similarly observed for the tricyclic antidepressants, phenothiazines, flurazepam and medazepam, with apparent Ki values ranging from 175 to 1000 microM. 4. Diclofenac and flufenamic acid were the only NSAIDs found to inhibit 4NP hydroxylation substantially; kinetic analysis was suggestive of activation-inhibition phenomena. 5. These data indicate that, although not substrates for CYP2E1, some clinically used drugs have the capacity to inhibit this enzyme and hence have the potential to modulate the toxicity of non-drug xenobiotics metabolized by CYP2E1.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Bifonazole Cytochrome P450 2E1 Protein Humans UnknownInhibitorDetails Bromazepam Cytochrome P450 2E1 Protein Humans UnknownInhibitorDetails Chlorpromazine Cytochrome P450 2E1 Protein Humans UnknownInhibitorDetails Clonazepam Cytochrome P450 2E1 Protein Humans UnknownInhibitorDetails Clotrimazole Cytochrome P450 2E1 Protein Humans UnknownInhibitorDetails Desipramine Cytochrome P450 2E1 Protein Humans UnknownInhibitorDetails Econazole Cytochrome P450 2E1 Protein Humans NoInhibitorDetails Flunitrazepam Cytochrome P450 2E1 Protein Humans UnknownInhibitorDetails Flurazepam Cytochrome P450 2E1 Protein Humans UnknownInhibitorDetails Itraconazole Cytochrome P450 2E1 Protein Humans NoInhibitorDetails Miconazole Cytochrome P450 2E1 Protein Humans UnknownInhibitorDetails Nitrazepam Cytochrome P450 2E1 Protein Humans UnknownInhibitorDetails Nortriptyline Cytochrome P450 2E1 Protein Humans UnknownInhibitorDetails - Drug Reactions
Reaction Details - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAcetaminophenQuercetin The metabolism of Acetaminophen can be decreased when combined with Quercetin. AcetaminophenNiacin The metabolism of Acetaminophen can be decreased when combined with Niacin. AcetaminophenDiosmin The metabolism of Acetaminophen can be decreased when combined with Diosmin. AcetaminophenCannabidiol The metabolism of Acetaminophen can be decreased when combined with Cannabidiol. AcetaminophenCannabinol The metabolism of Acetaminophen can be decreased when combined with Cannabinol.
