INT50405

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Context Info
Confidence 0.59
First Reported 1995
Last Reported 2010
Negated 0
Speculated 3
Reported most in Body
Documents 238
Total Number 241
Disease Relevance 53.65
Pain Relevance 51.51

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

small molecule metabolic process (CYP3A4) oxidoreductase activity (CYP3A4) endoplasmic reticulum (CYP3A4)
enzyme binding (CYP3A4) lipid metabolic process (CYP3A4) cytoplasm (CYP3A4)
Anatomy Link Frequency
liver 13
plasma 12
blood 3
enterocyte 2
1A2 2
CYP3A4 (Homo sapiens)
Pain Link Frequency Relevance Heat
Paracetamol 141 99.98 Very High Very High Very High
methadone 1577 99.96 Very High Very High Very High
fluoxetine 138 99.92 Very High Very High Very High
dexamethasone 269 99.90 Very High Very High Very High
Potency 207 99.72 Very High Very High Very High
Versed 485 99.68 Very High Very High Very High
Codeine 81 99.68 Very High Very High Very High
Buprenorphine 1069 99.62 Very High Very High Very High
lidocaine 195 99.50 Very High Very High Very High
antidepressant 158 99.50 Very High Very High Very High
Disease Link Frequency Relevance Heat
Toxicity 1698 99.90 Very High Very High Very High
Secondary Adrenal Insufficiency 5 99.76 Very High Very High Very High
Fungal Infection 93 99.68 Very High Very High Very High
Acquired Immune Deficiency Syndrome Or Hiv Infection 933 99.60 Very High Very High Very High
Cirrhosis 95 99.50 Very High Very High Very High
Pressure Volume 2 Under Development 142 99.36 Very High Very High Very High
Substance Withdrawal Syndrome 234 99.00 Very High Very High Very High
INFLAMMATION 195 98.88 Very High Very High Very High
Disease Progression 38 98.74 Very High Very High Very High
Disease 445 98.64 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
A number of clinically important drugs have been identified to be mechanism-based CYP3A4 inhibitors.
Negative_regulation (inhibitors) of CYP3A4
1) Confidence 0.59 Published 2004 Journal Curr. Drug Metab. Section Abstract Doc Link 15544435 Disease Relevance 0.09 Pain Relevance 0.18
Compared to reversible inhibition, mechanism-based inhibitors of CYP3A4 more frequently cause unfavorable drug-drug interactions, as the inactivated CYP3A4 has to be replaced by newly synthesized CYP3A4 protein.
Negative_regulation (inhibitors) of CYP3A4
2) Confidence 0.59 Published 2004 Journal Curr. Drug Metab. Section Abstract Doc Link 15544435 Disease Relevance 0.09 Pain Relevance 0.18
Rational use of drugs as mechanism-based CYP3A4 inhibitors
Negative_regulation (inhibitors) of CYP3A4
3) Confidence 0.59 Published 2005 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1661603 Disease Relevance 0.21 Pain Relevance 0
The clinical consequences of mechanism-based CYP3A4 inhibition depend upon additional factors.
Negative_regulation (inhibition) of CYP3A4
4) Confidence 0.59 Published 2005 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1661603 Disease Relevance 0 Pain Relevance 0.11
Irreversible inhibition of CYP3A4 due to enzyme inactivation or complexation occurs when some therapeutic drugs are converted by CYPs to reactive metabolites capable of covalently binding to CYP3A4 protein or heme moiety.
Negative_regulation (inhibition) of CYP3A4
5) Confidence 0.59 Published 2005 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1661603 Disease Relevance 0 Pain Relevance 0.07
Symptomatic hypotension may occur when mechanism-based CYP3A4 inhibitors are combined with some dihydropyridine calcium antagonists (Anderson and Nawarskas 2001), as well as with the phosphodiesterase inhibitor, sildenafil (Simonsen 2002).
Negative_regulation (inhibitors) of CYP3A4 associated with pressure volume 2 under development and antagonist
6) Confidence 0.59 Published 2005 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1661603 Disease Relevance 0.61 Pain Relevance 0.09
Clinical management of mechanism-based inhibition of CYP3A4
Negative_regulation (inhibition) of CYP3A4
7) Confidence 0.59 Published 2005 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1661603 Disease Relevance 0.08 Pain Relevance 0.05
By screening drug candidates for possible formation of reactive metabolic intermediates (MIs) that inhibit CYP3A4 in an irreversible manner, and by establishing structure-activity relationships, it is possible to identify and eliminate such chemicals at an early stage of development.
Spec (possible) Negative_regulation (inhibit) of CYP3A4
8) Confidence 0.59 Published 2005 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1661603 Disease Relevance 0.08 Pain Relevance 0
Generally, it can be anticipated that the inactivation of CYP3A4 by various drugs would increase the bioavailability of coadministered drugs that are primarily metabolized by CYP3A4, due to intestinal and/or hepatic inhibition of CYP3A4.
Negative_regulation (inhibition) of CYP3A4 associated with bioavailability
9) Confidence 0.59 Published 2005 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1661603 Disease Relevance 0 Pain Relevance 0.05
Identification of drugs causing irreversible CYP3A4 inhibition
Negative_regulation (inhibition) of CYP3A4
10) Confidence 0.59 Published 2005 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1661603 Disease Relevance 0.09 Pain Relevance 0
Mechanism-based inhibition of CYP3A4 can decrease a drug's first-pass clearance in the liver and greatly alter the kinetic behavior.
Negative_regulation (inhibition) of CYP3A4 in liver
11) Confidence 0.59 Published 2005 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1661603 Disease Relevance 0.08 Pain Relevance 0
A number of important drugs have been identified as substrates, inducers and/or inhibitors of CYP3A4.
Negative_regulation (inhibitors) of CYP3A4
12) Confidence 0.59 Published 2008 Journal Curr. Drug Metab. Section Abstract Doc Link 18473749 Disease Relevance 0.14 Pain Relevance 0.11
High concentrations of APAP inhibited CYP3A4 activity.
Negative_regulation (inhibited) of CYP3A4 associated with paracetamol
13) Confidence 0.59 Published 2002 Journal Arch. Biochem. Biophys. Section Abstract Doc Link 11811955 Disease Relevance 0 Pain Relevance 0.73
The interaction between amiodarone and lidocaine may be explained by the inhibition of CYP3A4 by amiodarone and/or by its main metabolite DEA.
Negative_regulation (inhibition) of CYP3A4 associated with lidocaine
14) Confidence 0.59 Published 1996 Journal J. Cardiovasc. Pharmacol. Section Abstract Doc Link 8891878 Disease Relevance 0 Pain Relevance 0.76
KTZ is also a potent inhibitor of human cytochrome P450 3A4 (CYP3A4) enzyme, the major drug-metabolizing CYP isozyme in the human liver.
Negative_regulation (inhibitor) of CYP3A4 in liver
15) Confidence 0.58 Published 2004 Journal Chirality Section Abstract Doc Link 14712470 Disease Relevance 0.50 Pain Relevance 0.15
Enantioselectivity of inhibition of cytochrome P450 3A4 (CYP3A4) by ketoconazole: Testosterone and methadone as substrates.
Negative_regulation (inhibition) of CYP3A4 associated with methadone
16) Confidence 0.58 Published 2004 Journal Chirality Section Title Doc Link 14712470 Disease Relevance 0.49 Pain Relevance 0.16
We examined the enantioselective differences of KTZ in the inhibition of human CYP3A4 and in antifungal action.
Negative_regulation (inhibition) of CYP3A4 associated with fungal infection
17) Confidence 0.58 Published 2004 Journal Chirality Section Abstract Doc Link 14712470 Disease Relevance 0.50 Pain Relevance 0.16
In contrast, capsiate, dihydrocapsiate, and nordihydrocapsiate did not inhibit cytochrome P450 3A4 activity and were unlikely to be mechanism-based inhibitors of CYP3A4.
Negative_regulation (inhibitors) of CYP3A4
18) Confidence 0.58 Published 2010 Journal Int. J. Toxicol. Section Abstract Doc Link 20388821 Disease Relevance 0 Pain Relevance 0.41
Studies suggest that amprenavir inhibits CYP3A4 to a greater extent than saquinavir, and to a much lesser extent than ritonavir.
Negative_regulation (inhibits) of CYP3A4
19) Confidence 0.58 Published 1998 Journal J Pharm Sci Section Abstract Doc Link 9649346 Disease Relevance 0.17 Pain Relevance 0.07
Metabolism of amprenavir in liver microsomes: role of CYP3A4 inhibition for drug interactions.
Negative_regulation (inhibition) of CYP3A4 in liver
20) Confidence 0.58 Published 1998 Journal J Pharm Sci Section Title Doc Link 9649346 Disease Relevance 0.16 Pain Relevance 0.09

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