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Grapefruit and grapefruit juice have been found to interact with numerous drugs (at least 85 known by 2013), in many cases resulting in adverse effects. Organic compounds that are furanocoumarin derivatives interfere with the hepatic and intestinal enzyme cytochrome P450 isoform CYP3A4 and are believed to be primarily responsible for the effects of grapefruit on the enzyme. Bioactive compounds in grapefruit juice may also interfere with P-glycoprotein and organic anion transporting polypeptides (OATPs), either increasing or decreasing the bioavailability of a number of drugs. Pomelo (the Asian fruit which was crossed with an orange to produce grapefruit) also contains high amounts of furanocoumarin derivatives. Grapefruit relatives and other pomelo descendants have variable amounts of furanocoumarins.〔Abstract:http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=175058 Fulltext:http://naldc.nal.usda.gov/download/1759/PDF〕〔(【引用サイトリンク】title=Hybrid grapefruit safe for prescription meds )〕 ==Affected drugs== Cytochrome isoforms affected by grapefruit components include CYP3A4, CYP1A2, CYP2C9, and CYP2D6. Drugs that are metabolized by these enzymes may have interactions with components of grapefruit. Drugs that interact with grapefruit compounds at the cytochrome P450 CYP3A4 isoform include: * The benzodiazepines triazolam (Halcion), orally administered midazolam (Versed), orally administered nitrazepam (Mogodon), certain amphetamines: dextroamphetamine and levoamphetamine (Dexedrine, Adderall, diazepam (Valium), alprazolam (Xanax) and quazepam (Doral, Dormalin) *ritonavir (Norvir): Inhibition of CYP3A4 prevents the metabolism of protease inhibitors such as ritonavir. * sertraline (Zoloft and Lustral) Drugs that interact with grapefruit compounds at the cytochrome P450 CYP1A2 isoform include: * Caffeine Drugs that interact with grapefruit compounds at the cytochrome P450 CYP2D6 isoform include: * dextroamphetamine (Dexedrine)〔 * levoamphetamine (Adderall) * methamphetamine (Desoxyn) Other stimulants that interact with the cytochrome P450 CYP2D6 enzyme include: * methylphenidate (Ritalin, Concerta) Research has been done on the interaction between amphetamines and the cytochrome P450 CYP2D6 enzyme, and researchers concluded that some parts of substrate molecules contribute to the binding of the enzyme.〔(【引用サイトリンク】title= Metabolism/ Metabolites of amphetamines interacting with The Cytochrome P450 CYP2D6 enzyme )〕 Additional drugs found to be affected by grapefruit juice include, but are not limited to: *Some statins, including atorvastatin (Lipitor),〔 〕 lovastatin (Mevacor) and simvastatin (Zocor, Simlup, Simcor, Simvacor) * * (In contrast, pravastatin〔 (Pravachol), fluvastatin (Lescol) and rosuvastatin (Crestor)〔 are unaffected by grapefruit.) *Anti-arrhythmics including amiodarone (Cordarone), dronedarone (Multaq), quinidine (Quinidex, Cardioquin, Quinora), disopyramide (Norpace), propafenone (Rythmol) and carvedilol (Coreg) *Anti-migraine drugs ergotamine (Cafergot, Ergomar), amitriptyline (Elavil, Endep, Vanatrip) and nimodipine (Nimotop)〔 *Erectile dysfunction drugs sildenafil (Viagra), tadalafil (Cialis) and vardenafil (Levitra)〔 *Acetaminophen/paracetamol (Tylenol) concentrations were found to be increased in murine blood by white and pink grapefruit juice, with the white juice acting faster. *Anthelmintics: Used for treating certain parasitic infections; includes praziquantel *Apremilast (Otezla) *Buprenorphine: Metabolized into norbuprenorphine by cytochrome-P450 isoenzyme 3A4 *Buspirone (Buspar): Grapefruit juice increased peak and AUC plasma concentrations of buspirone 4.3- and 9.2-fold, respectively, in a randomized, 2-phase, ten-subject crossover study. *Codeine *Cyclosporine (Neoral): Blood levels of cyclosporine are increased if taken with grapefruit juice. A plausible mechanism involves the combined inhibition of enteric CYP3A4 and P-glycoprotein, which potentially leads to serious adverse events (e.g., nephrotoxicity). Blood levels of tacrolimus (Prograf) can also be equally affected for the same reason as cyclosporine, as both drugs are calcineurin inhibitors. *Dihydropyridines including felodipine (Plendil), nicardipine (Cardene), nifedipine, nisoldipine (Sular) and nitrendipine (Bayotensin)〔 *Duloxetine (Cymbalta): May increase the risk of Serotonin Syndrome 〔http://www.medscape.org/viewarticle/550192〕 〔(【引用サイトリンク】title=Can I Eat Grapefruit While Taking Cymbalta? )〕 *Erlotinib (Tarceva) 〔(【引用サイトリンク】HIGHLIGHTS OF PRESCRIBING INFORMATION )〕 *Exemestane, aromasin, and by extension all estrogen-like compounds and aromatase inhibitors which mimic estrogen in function will be increased in effect, causing increased estrogen retention and increased drug retention.〔"http://www.macmillan.org.uk/Cancerinformation/Cancertreatment/Treatmenttypes/Hormonaltherapies/Individualhormonaltherapies/Exemestane.aspx〕 *Fexofenadine (Allegra) *Fluvoxamine (Luvox, Faverin, Fevarin and Dumyrox) *Imatinib (Gleevec): Although no formal studies with imatinib and grapefruit juice have been conducted, the fact that grapefruit juice is a known inhibitor of the CYP 3A4 suggests that co-administration may lead to increased imatinib plasma concentrations. Likewise, although no formal studies were conducted, co-administration of imatinib with another specific type of citrus juice called Seville orange juice (SOJ) may lead to increased imatinib plasma concentrations via inhibition of the CYP3A isoenzymes. Seville orange juice is not usually consumed as a juice because of its sour taste, but it is found in marmalade and other jams. Seville orange juice has been reported to be a possible inhibitor of CYP3A enzymes without affecting P-glycoprotein when taken concomitantly with cyclosporine.〔http://www.gistsupport.org/treatments-for-gist/gleevec/novartis-answers-about-gleevec.php〕 *Lamotrigine *Levothyroxine (Eltroxin, Levoxyl, Synthroid): the absorption of levothyroxine is affected by grapefruit juice. *Losartan (Cozaar)〔 *Methadone: Inhibits the metabolism of methadone and raises serum levels. *Omeprazole (Losec, Prilosec) *Oxycodone: metabolized by the cytochrome P450 system, specifically CYP3A4, of which the bergamottin flavonoid is a strong inhibitor *Quetiapine (Seroquel)〔(【引用サイトリンク】title=Grapefruit Interactions )〕 *Repaglinide (Prandin)〔 *Trazodone (Desyrel): Little or no interaction with grapefruit juice. *Verapamil (Calan SR, Covera HS, Isoptin SR, Verelan)〔 *Warfarin (coumadin)〔Jellin J.M., et al. Pharmacist's Letter/Prescriber's Letter of Natural Medicines Comprehensive Database. 7th ed. Stockton, CA: Therapeutic Research Faculty. 2005. 626-629〕 *Zolpidem (Ambien): Little or no interaction with grapefruit juice.〔 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Grapefruit–drug interactions」の詳細全文を読む スポンサード リンク
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