INT57923

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Context Info
Confidence 0.71
First Reported 1993
Last Reported 2010
Negated 0
Speculated 2
Reported most in Body
Documents 12
Total Number 14
Disease Relevance 2.62
Pain Relevance 2.00

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Anatomy Link Frequency
liver 2
feces 1
plasma 1
hepatocytes 1
brain 1
CYP3A (Homo sapiens)
Pain Link Frequency Relevance Heat
methadone 13 96.48 Very High Very High Very High
Bioavailability 48 94.92 High High
Versed 4 93.04 High High
Calcium channel 14 89.84 High High
rapifen 8 88.88 High High
Paracetamol 2 87.96 High High
Dextromethorphan 1 86.44 High High
Taxol 1 77.04 Quite High
ischemia 1 70.20 Quite High
analgesia 1 60.20 Quite High
Disease Link Frequency Relevance Heat
Pulmonary Hypertension 154 98.84 Very High Very High Very High
Adenocarcinoma 1 96.16 Very High Very High Very High
Hepatotoxicity 2 94.52 High High
Myocardial Infarction 9 91.84 High High
Pressure Volume 2 Under Development 4 91.64 High High
Disease 16 88.64 High High
Increased Venous Pressure Under Development 18 87.28 High High
Cancer 3 77.44 Quite High
Miosis 2 75.04 Quite High
Reperfusion Injury 1 70.96 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Formation of D-617 was correlated with the expression of CYP3A (r = 0.85; P < 0.001) and CYP1A2 (r = 0.57; P < 0.01) in the microsomal fraction of 21 human livers after incubation with racemic verapamil.
Gene_expression (expression) of CYP3A in livers
1) Confidence 0.71 Published 1993 Journal Naunyn Schmiedebergs Arch. Pharmacol. Section Abstract Doc Link 8232610 Disease Relevance 0 Pain Relevance 0
Chronic ritonavir inhibits hepatic CYP3A (> 70%) and first-pass CYP3A (> 90%).
Gene_expression (pass) of CYP3A
2) Confidence 0.66 Published 2008 Journal Clin. Pharmacol. Ther. Section Abstract Doc Link 19238656 Disease Relevance 0.08 Pain Relevance 0.46
Based on measured variability in CYP3A enzyme expression levels and plasma orosomucoid (ORM2) concentrations, a Monte-Carlo-based simulation of methadone kinetics in a pediatric population was performed.
Gene_expression (expression) of CYP3A in plasma associated with methadone
3) Confidence 0.63 Published 2006 Journal J Pharmacokinet Pharmacodyn Section Abstract Doc Link 16758333 Disease Relevance 0 Pain Relevance 0.86
Immunoblot analysis indicated the presence of enzymes related to cytochrome P450 (CYP) 1A1/CYP1A2, CYP2D6, CYP3A, and carboxylesterases (ESs) in human and monkey intestines, and of CYP3A and ES in dog intestines.
Gene_expression (presence) of CYP3A in intestines
4) Confidence 0.56 Published 1996 Journal Drug Metab. Dispos. Section Abstract Doc Link 8781778 Disease Relevance 0.10 Pain Relevance 0
Health effects were determined using a battery of end points indicative of growth effects [length, weight, condition factor, and hepatic expression of the gene for the somatotropic hormone insulin-like growth factor-1 (igf1)], genotoxicity (comet assay), immunotoxicity [differential white blood cell (WBC) count and phagocytotic activity of liver cells], and metabolic responses [hepatic ethoxy-resorufin-O-deethylase (EROD) activity and cytochrome P450 1a (cyp1a) and 3a (cyp3a) gene expression, as indicators of phase I bio-transformation, and glutathione S-transferase (gst) gene expression, as an indicator of phase II biotransformation].
Gene_expression (expression) of cyp3a in liver
5) Confidence 0.52 Published 2007 Journal Environ Health Perspect Section Body Doc Link PMC2137123 Disease Relevance 0 Pain Relevance 0
In this light, the objectives of our study were: 1) to determine the relative levels of CYP450 mRNAs (CYP1, CYP2, CYP3 and CYP4 families) in a large cohort (n?
Gene_expression (families) of CYP3
6) Confidence 0.46 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3001885 Disease Relevance 0.35 Pain Relevance 0.04
Hepatic expression of cyp3a was induced only by the potent estrogenic effluent (in both males and females) and not for any of the other treatments (Figure 4C).
Gene_expression (expression) of cyp3a
7) Confidence 0.41 Published 2007 Journal Environ Health Perspect Section Body Doc Link PMC2137123 Disease Relevance 0 Pain Relevance 0
Cremophor EL may inhibit PGP (p-glycoprotein), a relevant efflux pump which is expressed in high amount in gut, biliary tract and the blood brain barrier, and enzymes like CYP3A which may contribute to first pass metabolism.
Gene_expression (expressed) of CYP3A in brain
8) Confidence 0.33 Published 2007 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2374933 Disease Relevance 0 Pain Relevance 0.15
-OHC/C as a measure of CYP3A induction (Saima et al. 2002; Uejima et al. 2002; ELDesoky et al. 2005; Yeo et al. 2006).
Gene_expression (induction) of CYP3A
9) Confidence 0.32 Published 2006 Journal Biomark Insights Section Body Doc Link PMC2716776 Disease Relevance 0.76 Pain Relevance 0.11
CYP1A2, CYP2C9, CYP2D6, CYP2E1 and CYP3A activities were present at levels similar to human hepatocytes.
Gene_expression (present) of CYP3A in hepatocytes
10) Confidence 0.22 Published 2004 Journal Xenobiotica Section Abstract Doc Link 15204697 Disease Relevance 0 Pain Relevance 0.17
The mRNA expression levels of albumin and cytochrome P450 (CYP3A29) were determined by RT-PCR method.
Spec (determined) Gene_expression (expression) of CYP3A29
11) Confidence 0.09 Published 2005 Journal Biomed Mater Eng Section Abstract Doc Link 15912001 Disease Relevance 0 Pain Relevance 0.06
The mRNA expression levels of albumin and cytochrome P450 (CYP3A29) were determined by RT-PCR method.
Spec (determined) Gene_expression (levels) of CYP3A29
12) Confidence 0.07 Published 2005 Journal Biomed Mater Eng Section Abstract Doc Link 15912001 Disease Relevance 0 Pain Relevance 0.06
Tadalafil is predominantly metabolized by the liver by CYP3A and eliminated primarily in the feces and urine.50,51 Unlike sildenafil, it is recommended that patients with mild-to-moderate renal or hepatic dysfunction undergo a dose adjustment to 20 mg daily.31 As tadalafil is metabolized by CYP3A, inhibitors of the enzyme such as clarithromycin may lead to elevated serum concentrations.50 Combined usage of bosentan and tadalafil has been shown to lead to a 41.5% decrease in the serum levels of tadalafil with no effect on bosentan.52 Similar effects of combined use of tadalafil and ambrisentan have not been observed.53

PDE-5 inhibition for the treatment of PAH

Gene_expression (metabolized) of CYP3A in urine associated with pulmonary hypertension and hepatotoxicity
13) Confidence 0.07 Published 2010 Journal Vascular Health and Risk Management Section Body Doc Link PMC2868348 Disease Relevance 0.67 Pain Relevance 0.04
Tadalafil is predominantly metabolized by the liver by CYP3A and eliminated primarily in the feces and urine.50,51 Unlike sildenafil, it is recommended that patients with mild-to-moderate renal or hepatic dysfunction undergo a dose adjustment to 20 mg daily.31 As tadalafil is metabolized by CYP3A, inhibitors of the enzyme such as clarithromycin may lead to elevated serum concentrations.50 Combined usage of bosentan and tadalafil has been shown to lead to a 41.5% decrease in the serum levels of tadalafil with no effect on bosentan.52 Similar effects of combined use of tadalafil and ambrisentan have not been observed.53

PDE-5 inhibition for the treatment of PAH

Gene_expression (metabolized) of CYP3A in feces associated with pulmonary hypertension and hepatotoxicity
14) Confidence 0.02 Published 2010 Journal Vascular Health and Risk Management Section Body Doc Link PMC2868348 Disease Relevance 0.67 Pain Relevance 0.04

General Comments

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