INT47860
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Sentences Mentioned In
Key: | Protein | Mutation | Event | Anatomy | Negation | Speculation | Pain term | Disease term |
To determine the relative contributions of these P450's, overnight fasted male NMRI mice were pretreated with 10 ml of 50% v/w propylene glycol/kg or fluvoxamine (10 mg/kg) at -80 and -20 min. relative to acetaminophen dosing to inhibit CYP2E1 and CYP1A2, respectively. | |||||||||||||||
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Propylene glycol inhibited the activity of CYP2E1 as indicated by 84% reduction in the clearance of 3 mg/kg dose of chlorzoxazone, whereas fluvoxamine inhibited the activity of CYP1A2 as indicated by 40% reduction in the clearance of a 10 mg/kg dose of caffeine. | |||||||||||||||
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In beta-napthaflavone-pretreated mice, CYP1A2 activity was decreased only by the high dose of APAP, and covalent binding was > 2-fold higher at the high APAP dose. | |||||||||||||||
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Loss of CYP2E1 and CYP1A2 activity as a function of acetaminophen dose: relation to toxicity. | |||||||||||||||
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For example, mice lacking CYP1A2 and CYP2E1 are totally resistant to acetaminophen-induced hepatotoxicity. | |||||||||||||||
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Caffeine, an inhibitor of CYP1A2 activity and an enhancer of CYP3A activity, decreased APAP hepatotoxicity in wild-type mice. | |||||||||||||||
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Nefazodone is a weak inhibitor of cytochrome P450 (CYP) 2D6 and does not inhibit CYP1A2. | |||||||||||||||
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TAO treatment in vivo resulted in inhibition of microsomal CYP3A-catalyzed activity, measured in vitro, with no inhibition of CYP1A2 and CYP2E1 activities. | |||||||||||||||
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In non-induced mice, 150 mg/kg APAP caused minimal hepatotoxicity and loss of CYP2E1- but not CYP1A2-dependent activity. | |||||||||||||||
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Thus, the protection against APAP toxicity afforded by deletion of both CYP2E1 and CYP1A2 likely reflects greatly diminished production of the toxic electrophile, NAPQI. | |||||||||||||||
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In contrast, 400 mg/kg APAP was hepatotoxic and diminished both CYP2E1 and CYP1A2 activities. | |||||||||||||||
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The pretreatment regimen resulted in hepatic changes including: centrilobular localization of 3-(cysteine-S-yl)APAP protein adducts, selective down-regulation of cytochrome P4502E1 (CYP2E1) and CYP1A2 that produced the toxic metabolite, N-acetyl-p-benzoquinone imine, higher levels of reduced glutathione (GSH), centrilobular inflammation, and a fourfold increase in hepatocellular proliferation. | |||||||||||||||
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Analysis of phase I detoxification genes revealed that CYP1A2 and CYP3A11 were up-regulated in wild-type mice but down-regulated in RXRalpha-deficient mice after APAP administration. | |||||||||||||||
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The polymorphism of this subtype can induce loss-of-function to a considerable extent.25)26) Because CYP1A2 affects only the first oxidative step of clopidogrel, induction of CYP1A2 by smoking may have a relatively weak impact on clopidogrel activation.25)26) Furthermore, we assessed residual platelet reactivity at least 3 days after emergency stenting, which may be related to a decrease in smoking-induced CYP1A2 activity. | |||||||||||||||
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In primary human hepatocytes isolated from liver with macrosteatosis, there is a 60% to 40% reduction in 7-ethoxycoumarin O-deethylation (ECOD) and testosterone oxidation with a reduction in CYP1A2, CYP2C9, CYP2E1, and CYP3A4 mRNA and their respective proteins to metabolize their specific substrate drugs [107]. | |||||||||||||||
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Fluoxetine and paroxetine are potent inhibitors of CYP2D6, fluvoxamine markedly inhibits CYP1A2 and CYP2C19, while nefazodone is a potent inhibitor of CYP3A4. | |||||||||||||||
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Ciprofloxacine, an inhibitor of CYP1A2 did increase plasma levels of ropinirole when these two drugs were co-administered. | |||||||||||||||
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Because of its metabolism, the clearance is moderately reduced by CYP1A2 inhibitors such as fluvoxamine and CYP2D6 inhibitors such as fluoxetine, paroxetine and bupropion, and increased by CYP1A2 inducers such as carbamazepine (deLeon et al 2005). | |||||||||||||||
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Fluvoxamine inhibits oxidative drug metabolizing enzymes (particularly CYP1A2, and less potently, CYP3A4 and CYP2D6) and has the potential for clinically significant drug interactions.2 In the management of OCD, an array of different augmentation strategies may be employed in patients who exhibit only partial response to selective SRIs, including the use of clomipramine or of atypical antipsychotics as an add-on therapy.5 Clinicians should take into account the fact that fluvoxamine may lead to increased plasma levels of the augmentation drugs, either by inhibiting the CYP 1A2 (ie, haloperidol, olanzapine, and clomipramine) or the CYP3A4 (ie, haloperidol, pimozide, risperidone, quetiapine, and clomipramine). | |||||||||||||||
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Fluvoxamine is the only SSRI that is a potent inhibitor of cytochrome P4501A2 and hence causes serious pharmacokinetic interactions with amitriptyline, clomipramine, imipramine, theophylline, and presumably caffeine and other drugs which are metabolized by the isozyme. | |||||||||||||||
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