INT50580

Context Info Confidence 0.36 First Reported 1995 Last Reported 2010 Negated 2 Speculated 0 Reported most in Abstract Documents 39 Total Number 39 Disease Relevance 11.17 Pain Relevance 12.34

isomerase activity (PPIG) protein folding (PPIG) nucleoplasm (PPIG) nucleolus (PPIG) nucleus (PPIG) cytoplasm (PPIG)

Anatomy Link Frequency 1A2 4 plasma 3 liver 3 hair 1 bladder 1 PPIG (Homo sapiens)

Pain Link Frequency Relevance Heat monoamine 18 100.00 lidocaine 13 99.96 Duloxetine 139 99.92 methadone 110 99.92 MU agonist 1 99.58 Paracetamol 16 99.36 aspirin 23 99.32 Bioavailability 25 99.08 Versed 17 98.92 Buprenorphine 64 98.88

Disease Link Frequency Relevance Heat Hepatotoxicity 26 99.58 Death 20 99.50 Cv Unclassified Under Development 2 99.38 Renal Failure 13 99.30 Sepsis 9 99.08 Pressure And Volume Under Development 8 99.06 Organ Transplantation 1 98.16 Recurrence 108 96.12 Renal Disease 19 96.12 Necrosis 10 96.12

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

In these trials, duloxetine increased blood pressure in a dose-dependent manner. (7) Duloxetine is metabolized by cytochrome P450 isoenzymes CYP 1A2 and CYP 2D6, creating an important risk of interactions with other drugs. (8) In practice, duloxetine currently has no place in the treatment of depression or diabetic neuropathy.

CYP Binding (metabolized) of in 1A2 associated with pressure and volume under development, depression, diabetic neuropathy and duloxetine

1) Confidence 0.36 Published 2006 Journal Prescrire Int Section Abstract Doc Link 17121211 Disease Relevance 0.98 Pain Relevance 1.08

Some HMG CoA reductase inhibitors have the ability to inhibit the CYP 3A4 enzyme, which can result in a possible interaction if administered concomitantly with clopidogrel.

CYP Binding (interaction) of

2) Confidence 0.36 Published 2006 Journal J. Thromb. Thrombolysis Section Abstract Doc Link 17008981 Disease Relevance 0.08 Pain Relevance 0.63

Cytochrome P450 (CYP) 3A4 is not only the most abundant isoform in human liver but also metabolizes approximately 60% of the therapeutic drugs.

CYP Binding (metabolizes) of in liver

3) Confidence 0.36 Published 2004 Journal Curr. Drug Metab. Section Abstract Doc Link 15544435 Disease Relevance 0 Pain Relevance 0

It is an inhibitor of cytochrome P450 (CYP) 2D6 and other CYP enzymes, which increases the potential for drug interactions.

CYP Binding (interactions) of

4) Confidence 0.36 Published 2004 Journal Expert Opin Drug Saf Section Abstract Doc Link 15335304 Disease Relevance 0.08 Pain Relevance 0.45

In these trials, duloxetine increased blood pressure in a dose-dependent manner. (7) Duloxetine is metabolized by cytochrome P450 isoenzymes CYP 1A2 and CYP 2D6, creating an important risk of interactions with other drugs. (8) In practice, duloxetine currently has no place in the treatment of depression or diabetic neuropathy.

CYP Binding (metabolized) of in 1A2 associated with pressure and volume under development, depression, diabetic neuropathy and duloxetine

5) Confidence 0.36 Published 2006 Journal Prescrire Int Section Abstract Doc Link 17121211 Disease Relevance 0.98 Pain Relevance 1.08

The activity of hCAR is regulated by a variety of xenobiotics including clotrimazole and acetaminophen metabolites. hCAR, in turn, regulates a number of genes responsible for xenobiotic metabolism and transport including several cytochrome P450s (CYP 2B5, 2C9, and 3A4) and the multidrug resistance-associated protein 2 (MRP2, ABCC2).

CYP Binding (metabolism) of in 2B5 associated with paracetamol

6) Confidence 0.36 Published 2003 Journal Mol. Genet. Metab. Section Abstract Doc Link 14567971 Disease Relevance 0 Pain Relevance 0.10

BACKGROUND AND OBJECTIVES: Acetaminophen (INN, paracetamol) is metabolized to N-acetyl-p-benzoquinone imine (NAPQI), a hepatotoxic metabolite, predominantly by cytochrome P450 (CYP) 2E1.

CYP Binding (metabolized) of associated with paracetamol

7) Confidence 0.36 Published 2003 Journal Clin. Pharmacol. Ther. Section Abstract Doc Link 12811364 Disease Relevance 0.10 Pain Relevance 0.37

DRUG INTERACTIONS: Coformulated lopinavir/ritonavir has the potential to interact with wide variety of drugs via several mechanisms, mostly involving the CYP enzymes.

CYP Binding (interact) of

8) Confidence 0.36 Published 2003 Journal Drugs Section Abstract Doc Link 12662125 Disease Relevance 0.20 Pain Relevance 0.07

Etoricoxib is partly metabolised by the cytochrome P450 isoenzyme CYP 3A4 and increases the bioavailability of ethinylestradiol. (7) When a NSAID is considered, drugs with which we have the most experience should be chosen, such as ibuprofen, and used at the lowest acceptable dose regimen (daily dose and length of treatment).

CYP Binding (metabolised) of associated with cinod and bioavailability

9) Confidence 0.36 Published 2007 Journal Prescrire Int Section Abstract Doc Link 18084859 Disease Relevance 0.73 Pain Relevance 0.72

Although pravastatin has lower potency than other described statins, it also has the lowest risk of drug-drug interactions involving CYP.

CYP Binding (interactions) of associated with potency

10) Confidence 0.36 Published 2008 Journal Drugs Aging Section Abstract Doc Link 18665658 Disease Relevance 0.68 Pain Relevance 0.17

Other advantages of genotyping over traditional TDM include, but are not limited to, the following: (i) it does not require the assumption of steady-state conditions (or patient compliance) for the interpretation of results; (ii) it can often be performed less invasively (with saliva, hair root or buccal swab samples); (iii) it can provide predictive value for multiple drugs [e.g. a number of cytochrome P450 (CYP) 2D6, CYP2C 19 or CYP2C9 substrates] rather than a single drug; (iv) it provides mechanistic, instead of merely descriptive, information; and (v) it is constant over an individual's lifetime (and not influenced by concurrent drug administration, alteration in hormonal levels or disease states).

CYP Binding (number) of in hair associated with disease

11) Confidence 0.36 Published 2001 Journal Clin Pharmacokinet Section Abstract Doc Link 11735602 Disease Relevance 0.09 Pain Relevance 0

The patient should be closely monitored if he or she is taking several medications that may inhibit or induce the CYP 1A2 isoenzyme.

CYP Binding (induce) of in 1A2

12) Confidence 0.36 Published 1999 Journal J Gend Specif Med Section Abstract Doc Link 11252858 Disease Relevance 0.55 Pain Relevance 0.09

Differences in the metabolic balance between hepatic P450 (especially CYP 1A2) and MAO-A inactivation lead to potential drug interactions for all TELs with the oral contraceptive pill (OCP), fluvoxamine and the quinilone antibiotics (with increased triptan levels).

CYP Binding (interactions) of in 1A2 associated with triptan

13) Confidence 0.36 Published 2000 Journal Expert Opin Pharmacother Section Abstract Doc Link 11249525 Disease Relevance 0.13 Pain Relevance 0.81

Reboxetine at therapeutic concentrations has no effect on the in vitro activity of CYP1A2, 2C9, 2D6, 2E1 or 3A4.

CYP Neg (no) Binding (activity) of

14) Confidence 0.36 Published 2000 Journal Clin Pharmacokinet Section Abstract Doc Link 11192474 Disease Relevance 0.15 Pain Relevance 0.18

Cytochrome P450 (CYP) 2D6 is one of the most investigated CYPs in relation to genetic polymorphism, but accounts for only a small percentage of all hepatic CYPs (approximately 2-4%).

CYP Binding (accounts) of

15) Confidence 0.36 Published 2009 Journal Clin Pharmacokinet Section Abstract Doc Link 19817501 Disease Relevance 0.07 Pain Relevance 0.21

Clopidogrel is metabolized to an active thiol metabolite by the CYP 3A4 enzyme.

CYP Binding (metabolized) of

16) Confidence 0.36 Published 2006 Journal J. Thromb. Thrombolysis Section Abstract Doc Link 17008981 Disease Relevance 0.08 Pain Relevance 0.64

Pharmacokinetic interactions can involve CYP 2D6, which acts on drugs such as codeine and is responsible for its conversion to morphine.

CYP Binding (interactions) of

17) Confidence 0.31 Published 2000 Journal J. Clin. Oncol. Section Body Doc Link 10764440 Disease Relevance 0 Pain Relevance 0

Rifampicin has been shown to induce CYP3A4, a major human hepatic CYP isozyme that is known to metabolize lidocaine to its primary metabolite, monoethylglycinexylidide.

CYP Binding (metabolize) of associated with lidocaine

18) Confidence 0.30 Published 1995 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 7636727 Disease Relevance 0 Pain Relevance 0.40

RESULTS: A concentration-dependent decrease in luminescence signal was detected for ibuprofen and diclofenac in the assay for CYP 2C9 in human and equine liver microsomes but not in the assay for CYP 3A4 and methadone or xylazine in any of the species.

CYP Binding (assay) of in liver

19) Confidence 0.23 Published 2009 Journal Am. J. Vet. Res. Section Body Doc Link 19496669 Disease Relevance 0 Pain Relevance 0

Hence, the likelihood of a clinically-important drug interaction with CYP isozyme 2D6 substrates and trospium chloride is very low (Anonymous 2004).

CYP Binding (interaction) of

20) Confidence 0.16 Published 2005 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1661617 Disease Relevance 0.26 Pain Relevance 0.10

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