同: cytochrome C450 2C9

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/10/15 22:55:01」(JST)

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Cytochrome P450 2C9 (abbreviated CYP2C9) is an enzyme that in humans is encoded by the CYP2C9 gene.^[1]^[2]

Function[edit]

CYP2C9 is an important cytochrome P450 enzyme with a major role in the oxidation of both xenobiotic and endogenous compounds. CYP2C9 makes up about 18% of the cytochrome P450 protein in liver microsomes (data only for antifungal). Some 100 therapeutic drugs are metabolized by CYP2C9, including drugs with a narrow therapeutic index such as warfarin and phenytoin and other routinely prescribed drugs such as acenocoumarol, tolbutamide, losartan, glipizide, and some nonsteroidal anti-inflammatory drugs. By contrast, the known extrahepatic CYP2C9 often metabolizes important endogenous compound such as arachidonic acid, 5-hydroxytryptamine, and linoleic acid.^[3]

Pharmacogenomics[edit]

Genetic polymorphism exists for CYP2C9 expression because the CYP2C9 gene is highly polymorphic. More than 50 single nucleotide polymorphisms (SNPs) have been described in the regulatory and coding regions of the CYP2C9 gene,^[4] some of them are associated with reduced enzyme activity compared with wild type in vitro.^{[citation needed]}

Multiple in vivo studies also show that several mutant CYP2C9 genotypes are associated with significant reduction of in metabolism and daily dose requirements of selected CYP2C9 substrate. In fact, adverse drug reactions (ADRs) often result from unanticipated changes in CYP2C9 enzyme activity secondary to genetic polymorphisms. Especially for CYP2C9 substrates such as warfarin and phenytoin, diminished metabolic capacity because of genetic polymorphisms or drug-drug interactions can lead to toxicity at normal therapeutic doses.^[5]^[6]

Allele frequencies(%) of CYP2C9 polymorphism

	African-American	Black-African	Pygmy	Asian	Caucasian
CYP2C9*2	2.9	0-4.3	0	0-0.1	8-19
CYP2C9*3	2.0	0-2.3	0	1.1-3.6	3.3-16.2
CYP2C9*5	0-1.7	0.8-1.8	ND	0	0
CYP2C9*6	0.6	2.7	ND	0	0
CYP2C9*7	0	0	6	0	0
CYP2C9*8	1.9	8.6	4	0	0
CYP2C9*9	13	15.7	22	0	0.3
CYP2C9*11	1.4-1.8	2.7	6	0	0.4-1.0
CYP2C9*13	ND	ND	ND	0.19-0.45	ND

CYP2C9 Ligands[edit]

Most inhibitors of CYP2C9 are competitive inhibitors. Noncompetitive inhibitors of CYP2C9 include nifedipine,^[7]^[8] phenethyl isothiocyanate,^[9] medroxyprogesterone acetate^[10] and 6-hydroxyflavone. It was indicated that the noncompetitive binding site of 6-hydroxyflavone is the reported allosteric binding site of the CYP2C9 enzyme.^[11]

Following is a table of selected substrates, inducers and inhibitors of CYP2C9. Where classes of agents are listed, there may be exceptions within the class.

Inhibitors of CYP2C9 can be classified by their potency, such as:

Strong being one that causes at least a 5-fold increase in the plasma AUC values, or more than 80% decrease in clearance.^[12]
Moderate being one that causes at least a 2-fold increase in the plasma AUC values, or 50-80% decrease in clearance.^[12]
Weak being one that causes at least a 1.25-fold but less than 2-fold increase in the plasma AUC values, or 20-50% decrease in clearance.^[12]

**Selected inducers, inhibitors and substrates of CYP2C9**
Substrates	Inhibitors	Inducers
NSAIDs (analgesic, antipyretic, anti-inflammatory) celecoxib^[12]^[13] lornoxicam^[12]^[14] diclofenac^[12]^[13] ibuprofen ^[12]^[13] naproxen^[12]^[13] ketoprofen^[15] piroxicam^[12]^[13] meloxicam^[12]^[13] suprofen^[12] phenytoin^[12]^[13] (antiepileptic) fluvastatin^[12]^[13] (statin) sulfonylureas (antidiabetic) glipizide^[12]^[13] glibenclamide^[12]^[13] glimepiride^[12]^[13] tolbutamide^[12]^[12] glyburide^[12] angiotensin II receptor antagonists (in hypertension, diabetic nephropathy, CHF) irbesartan^[12]^[13] losartan^[12]^[13] S-warfarin^[12]^[13] (anticoagulant) sildenafil^[13] (in erectile dysfunction) terbinafine^[13] (antifungal) amitriptyline^[12] (tricyclic antidepressant) fluoxetine^[12] (SSRI antidepressant) nateglinide^[12] (antidiabetic) rosiglitazone^[12] (antidiabetic) tamoxifen^[12] (SERM) torasemide^[12] (loop diuretic) ketamine	Strong: fluconazole^[12]^[13] (antifungal) miconazole^[13] (antifungal) amentoflavone^[16] (constituent of Ginkgo biloba and St. John’s Wort^[17] sulfaphenazole^[13] (antibacterial) Valproic acid^[13] (anticonvulsant, mood-stabilizing) Apigenin^[11] Moderate amiodarone^[12] (antiarrhythmic) Unspecified potency antihistamines (H1-receptor antagonists) Cyclizine^[18] Promethazine^[18] Chloramphenicol^[19] fenofibrate^[12] (fibrate) flavones^[11] flavonols^[11] fluvastatin^[12] (statin) fluvoxamine^[12] (SSRI) isoniazid^[12] (in tuberculosis) lovastatin^[12] (statin) phenylbutazone^[12] (NSAID) probenecid^[12] (uricosuric) sertraline^[12] (SSRI) sulfamethoxazole^[12] (antibiotic) teniposide^[12] (chemotherapeutic) voriconazole^[12] (antifungal) zafirlukast^[12] (leukotriene antagonist) quercetin^[11] (anti-inflammatory)	Strong: rifampicin^[12]^[13] (bactericidal) secobarbital^[12] (barbiturate)

References[edit]

^ Romkes M, Faletto MB, Blaisdell JA, Raucy JL, Goldstein JA (April 1991). "Cloning and expression of complementary DNAs for multiple members of the human cytochrome P450IIC subfamily". Biochemistry 30 (13): 3247–55. doi:10.1021/bi00227a012. PMID 2009263.
^ Inoue K, Inazawa J, Suzuki Y, Shimada T, Yamazaki H, Guengerich FP, Abe T (September 1994). "Fluorescence in situ hybridization analysis of chromosomal localization of three human cytochrome P450 2C genes (CYP2C8, 2C9, and 2C10) at 10q24.1". Jpn. J. Hum. Genet. 39 (3): 337–43. doi:10.1007/BF01874052. PMID 7841444.
^ Rettie AE, Jones JP (2005). "Clinical and toxicological relevance of CYP2C9: drug-drug interactions and pharmacogenetics". Annu. Rev. Pharmacol. Toxicol. 45: 477–94. doi:10.1146/annurev.pharmtox.45.120403.095821. PMID 15822186.
^ Sim, Sarah C (2-May-2011). "CYP2C9 allele nomenclature". Cytochrome P450 (CYP) Allele Nomenclature Committee. ^{[self-published source?]}
^ García-Martín E, Martínez C, Ladero JM, Agúndez JA (2006). "Interethnic and intraethnic variability of CYP2C8 and CYP2C9 polymorphisms in healthy individuals". Mol Diagn Ther 10 (1): 29–40. doi:10.1007/BF03256440. PMID 16646575.
^ Rosemary J, Adithan C (January 2007). "The pharmacogenetics of CYP2C9 and CYP2C19: ethnic variation and clinical significance". Curr Clin Pharmacol 2 (1): 93–109. doi:10.2174/157488407779422302. PMID 18690857.
^ Bourrié M, Meunier V, Berger Y, Fabre G (February 1999). "Role of cytochrome P-4502C9 in irbesartan oxidation by human liver microsomes". Drug Metab. Dispos. 27 (2): 288–96. PMID 9929518.
^ Salsali M, Holt A, Baker GB (February 2004). "Inhibitory effects of the monoamine oxidase inhibitor tranylcypromine on the cytochrome P450 enzymes CYP2C19, CYP2C9, and CYP2D6". Cell. Mol. Neurobiol. 24 (1): 63–76. doi:10.1023/B:CEMN.0000012725.31108.4a. PMID 15049511.
^ Nakajima M, Yoshida R, Shimada N, Yamazaki H, Yokoi T (August 2001). "Inhibition and inactivation of human cytochrome P450 isoforms by phenethyl isothiocyanate". Drug Metab. Dispos. 29 (8): 1110–3. PMID 11454729.
^ Zhang JW, Liu Y, Li W, Hao DC, Yang L (July 2006). "Inhibitory effect of medroxyprogesterone acetate on human liver cytochrome P450 enzymes". Eur. J. Clin. Pharmacol. 62 (7): 497–502. doi:10.1007/s00228-006-0128-9. PMID 16645869.
^ ^a ^b ^c ^d ^e Si D, Wang Y, Zhou YH, Guo Y, Wang J, Zhou H, Li ZS, Fawcett JP (March 2009). "Mechanism of CYP2C9 inhibition by flavones and flavonols". Drug Metab. Dispos. 37 (3): 629–34. doi:10.1124/dmd.108.023416. PMID 19074529.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t ^u ^v ^w ^x ^y ^z ^aa ^ab ^ac ^ad ^ae ^af ^ag ^ah ^ai ^aj ^ak ^al ^am ^an ^ao ^ap ^aq ^ar Flockhart DA (2007). "Drug Interactions: Cytochrome P450 Drug Interaction Table". Indiana University School of Medicine.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t ^u FASS (drug formulary): "Facts for prescribers (Fakta för förskrivare)". Swedish environmental classification of pharmaceuticals (in Swedish).
^ Guo Y, Zhang Y, Wang Y, Chen X, Si D, Zhong D, Fawcett JP, Zhou H (June 2005). "Role of CYP2C9 and its variants (CYP2C9*3 and CYP2C9*13) in the metabolism of lornoxicam in humans". Drug Metab. Dispos. 33 (6): 749–53. doi:10.1124/dmd.105.003616. PMID 15764711.
^ http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3825&loc=ec_rcs#x301
^ Kimura Y, Ito H, Ohnishi R, Hatano T (January 2010). "Inhibitory effects of polyphenols on human cytochrome P450 3A4 and 2C9 activity". Food Chem. Toxicol. 48 (1): 429–35. doi:10.1016/j.fct.2009.10.041. PMID 19883715.
^ Pan X, Tan N, Zeng G, Zhang Y, Jia R (October 2005). "Amentoflavone and its derivatives as novel natural inhibitors of human Cathepsin B". Bioorg. Med. Chem. 13 (20): 5819–25. doi:10.1016/j.bmc.2005.05.071. PMID 16084098.
^ ^a ^b He N, Zhang WQ, Shockley D, Edeki T (February 2002). "Inhibitory effects of H1-antihistamines on CYP2D6- and CYP2C9-mediated drug metabolic reactions in human liver microsomes". Eur. J. Clin. Pharmacol. 57 (12): 847–51. doi:10.1007/s00228-001-0399-0. PMID 11936702.
^ Park JY, Kim KA, Kim SL (November 2003). "Chloramphenicol is a potent inhibitor of cytochrome P450 isoforms CYP2C19 and CYP3A4 in human liver microsomes". Antimicrob. Agents Chemother. 47 (11): 3464–9. doi:10.1128/AAC.47.11.3464-3469.2003. PMC 253795. PMID 14576103.

External links[edit]

PharmGKB: Annotated PGx Gene Information for CYP2C9
SuperCYP: Database for Drug-Cytochrome-Interactions

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 薬理ゲノム学の概要 overview of pharmacogenomics
2. ワルファリンおよびその他のビタミンK拮抗剤の治療使用 therapeutic use of warfarin and other vitamin k antagonists
3. オーダーメイド医療 personalized medicine
4. 重症筋無力症に対する長期免疫療法 chronic immunomodulating therapies for myasthenia gravis
5. リファマイシン（リファンピン、リファブチン、リファペンチン） rifamycins rifampin rifabutin rifapentine

English Journal

Comparative in vitro metabolism of phospho-tyrosol-indomethacin by mice, rats and humans.

Xie G, Zhou D, Cheng KW, Wong CC, Rigas B.SourceDivision of Cancer Prevention, Department of Medicine, Stony Brook University, HSC, T17-080, Stony Brook, NY 11794, USA. Electronic address: basil.rigas@stonybrook.edu.
Biochemical pharmacology.Biochem Pharmacol.2013 Apr 15;85(8):1195-202. doi: 10.1016/j.bcp.2013.01.031. Epub 2013 Feb 8.
Phospho-tyrosol-indomethacin (PTI; MPI 621), a novel anti-cancer agent, is more potent and safer than conventional indomethacin. Here, we show that PTI was extensively metabolized in vitro and in vivo. PTI was rapidly hydrolyzed by carboxylesterases to generate indomethacin as its major metabolite i
PMID 23399640

CYP3A4 and CYP2C19 genetic polymorphisms and zolpidem metabolism in the Chinese Han population: A pilot study.

Shen M, Shi Y, Xiang P.SourceShanghai Key Laboratory of Forensic Medicine, Department of Forensic Toxicology, Institute of Forensic Science, Ministry of Justice, Guangfu Xi Road 1347, Shanghai 200063, PR China. Electronic address: minshensfjd@hotmail.com.
Forensic science international.Forensic Sci Int.2013 Apr 10;227(1-3):77-81. doi: 10.1016/j.forsciint.2012.08.035. Epub 2012 Sep 8.
Zolpidem (ZPD) is an imidazopyridine hypnotic and little is known about the pharmacogenetics of ZPD. Our objective was to evaluate inter-individual genetic variation in conjunction with metabolic ratios of ZPD found in a toxicological analysis. Healthy individuals (n=300) were genotyped for CYP2D6,
PMID 22964165

Japanese Journal

日本人ワルファリン服用者でのCYP2C9とVKORC1の遺伝子一塩基多型解析の臨床的意義(岩手医科大学学位審査報告)

宮形養
岩手医科大学歯学雑誌 36(2), 128-129, 2011-08-19
NAID 110008733450

Polymorphism of warfarin related genes (VKORC1 and CYP2C9) analyzed by the smart amplification process method in patients with atrial fibrillation

Watanabe Minoru,Matsumoto Naoki,Kumai Toshio [他]
Journal of St. Marianna University 2(1), 25-29, 2011-06
NAID 40018916870

Proposal of pharmacogenetics-based warfarin dosing algorithm in Korean patients

Choi Jung Ran,Kim Jeong-Oh,Kang Dae Ryong [他]
Journal of human genetics 56(4), 290-295, 2011-04
NAID 40018765628

Related Pictures

CYP2C9 Haplotype Structure and Association Get to Know an Enzyme: CYP2C9 CYP2C9. Fluconazole, at conventional doses rose cyp2c9 1r9o homo sapiens green CYP2C9 Slide. CYP2C9 Substrates Ribbon diagram of CYP2C9,

★リンクテーブル★

リンク元	「HMG-CoA還元酵素阻害薬」「フルコナゾール」

「HMG-CoA還元酵素阻害薬」

Cytochrome P450, family 2, subfamily C, polypeptide 9
	; Ribbon diagram of CYP2C9, heme group visible at center. From PDB 1OG2.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1OG2, 1OG5, 1R9O
Identifiers
Symbols	CYP2C9; CPC9; CYP2C; CYP2C10; CYPIIC9; P450IIC9
External IDs	OMIM: 601130 MGI: 103238 HomoloGene: 128042 ChEMBL: 3397 GeneCards: CYP2C9 Gene
EC number	1.14.13.48, 1.14.13.49, 1.14.13.80
Gene Ontology
Molecular function	• monooxygenase activity; • iron ion binding; • drug binding; • steroid hydroxylase activity; • electron carrier activity; • oxidoreductase activity; • (S)-limonene 6-monooxygenase activity; • (S)-limonene 7-monooxygenase activity; • heme binding; • caffeine oxidase activity; • (R)-limonene 6-monooxygenase activity;
Cellular component	• endoplasmic reticulum; • endoplasmic reticulum membrane; • intracellular membrane-bounded organelle;
Biological process	• xenobiotic metabolic process; • steroid metabolic process; • monoterpenoid metabolic process; • drug metabolic process; • arachidonic acid metabolic process; • epoxygenase P450 pathway; • urea metabolic process; • monocarboxylic acid metabolic process; • drug catabolic process; • exogenous drug catabolic process; • cellular amide metabolic process; • small molecule metabolic process; • oxidation-reduction process; • oxidative demethylation; • omega-hydroxylase P450 pathway;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	This box: view; talk; edit;

　　[★]

英: HMG-CoA reductase inhibitor
同: ヒドロキシメチルグルタリルコエンザイムA還元酵素阻害薬 hydroxymethylglutaryl-CoA reductase inhibitor。スタチン statin
関: 高脂血症治療薬、高脂血症、コレステロールの生合成。HMG-CoA還元酵素 HMG-CoA reductase

特徴

強力なコレステロール低下作用

アトルバスタチンの場合

血清TC低下率30%

血清LDL-C低下率41%

血清TG低下作用

TG250-350mg/dl　380

TG350-450mg/dl　470

安全性が高い(プラバスタチンのみ)

プラバスタチンは水溶性。(⇔脂溶性だとどこでも入っていく→全身性に作用する)

プラバスタチンの輸送担体は肝臓にしかない→臓器選択性↑→安全性↑

CYP3A4との相互作用がない

種類

CYP 代謝による分類	薬物	商品名	性質1)		CYP代謝 2)	代謝物の活性 3)	排泄形態 3)	bioavailability (%) 3)	尿中排泄 (%) 2)	半減期 (hr) 2)
CYP 代謝による分類	薬物	商品名	定性	定量(LogP)	CYP代謝 2)	代謝物の活性 3)	排泄形態 3)	bioavailability (%) 3)	尿中排泄 (%) 2)	半減期 (hr) 2)
非代謝型	プラバスタチン	メバロチン	水溶性	-0.47	ほとんどなし	ー	未変化体	18	20	1ー2
	ロスバスタチン	クレストール	水溶性			ー 5)	未変化体 5)	29	10 5)	15～19 5)
	ピタバスタチン	リバロ	脂溶性	1.49		ー	未変化体	60	＜2	11
代謝型	フルバスタチン	ローコール	脂溶性	1.73	CYP2C9	なし	代謝物	10-35	＜6	1.2
	シンバスタチン	リポバス	脂溶性	4.4	CYP3A4	あり	代謝物	＜5	13	1ー2
	アトルバスタチン	リピトール	脂溶性	1.53	CYP3A4	あり	(データ無し)	12	2	14
1)Prog Med, 18:957-962,1998. 2)Heart, 85:259-264,2001. 3)PHarmacol Ther, 80:1-34 改変 4)興和(株)社内資料 5)添付文書

作用機序

HMG-CoA reductaseを競合阻害→肝内コレステロール産生↓→肝LDL受容体発現↑→血中LDL↓

HMG-CoA reductaseはHMG-CoAからmevalonate産生を触媒

副作用

1. 横紋筋融解症

原因：メバロン酸合成↓→CoQ↓→ミトコンドリア機能異常。Cl^-の細胞膜透過性の変化

2. CYPを介する薬物相互作用

CYP	代謝されるスタチン	代謝される薬物	強く阻害する薬物
CYP2C9	フルバスタチン	ワーファリンジクロフェナクフェニトイン	サルファ剤 ST合剤
CYP3A4	シンバスタチンセリバスタチンアトルバスタチン	ニフェジピンシクロスポリンジルチアゼムなど多数	エリスロマイシンシメチジンイトラコナゾールベラパミル

薬物相互作用によりCYP3A4の働きが阻害されると、横紋筋融解症の引き金となりうる

3. 肝障害

脂溶性HMG-CoA還元酵素阻害薬は重篤な肝障害を起こす

4. CK上昇

This was suggested by a study showing greater increases in post-marathon CK levels in individuals receiving statins; older runners receiving statins exhibited more susceptibility to CK elevations than younger runners. These elevations in CK were, however, mild and subclinical, which suggests that trained individuals need not discontinue statin therapy prior to a race.(uptodate)

軽度であれば(マラソンの)習熟者はレース前にスタチンを中止をする必要がないことを示唆する。

禁忌

妊婦

「フルコナゾール」

　　[★]

英: fluconazole
同: FLCZ
商: ジフルカン、ニコアゾリン、ビスカルツ、フラノス、フルカード、フルカジール、フルコナゾン、フルタンゾール、ミコシスト
関: 抗真菌薬

抗真菌薬

アゾール系

トリアゾール系

ADME

阻害

CYP2C9, CYP2C19, CYP3A4

排泄

大部分が腎臓から排泄される

添付文書

ジフルカンカプセル50mg／ジフルカンカプセル100mg

http://www.info.pmda.go.jp/go/pack/6290002M1020_2_01/6290002M1020_2_01?view=body

ジフルカン静注液50mg／ジフルカン静注液100mg／ジフルカン...

http://www.info.pmda.go.jp/go/pack/6290401A1099_2_01/6290401A1099_2_01?view=body

[pmid2009263-1] Romkes M, Faletto MB, Blaisdell JA, Raucy JL, Goldstein JA (April 1991). "Cloning and expression of complementary DNAs for multiple members of the human cytochrome P450IIC subfamily". Biochemistry 30 (13): 3247–55. doi:10.1021/bi00227a012. PMID 2009263.

[pmid7841444-2] Inoue K, Inazawa J, Suzuki Y, Shimada T, Yamazaki H, Guengerich FP, Abe T (September 1994). "Fluorescence in situ hybridization analysis of chromosomal localization of three human cytochrome P450 2C genes (CYP2C8, 2C9, and 2C10) at 10q24.1". Jpn. J. Hum. Genet. 39 (3): 337–43. doi:10.1007/BF01874052. PMID 7841444.

[pmid15822186-3] Rettie AE, Jones JP (2005). "Clinical and toxicological relevance of CYP2C9: drug-drug interactions and pharmacogenetics". Annu. Rev. Pharmacol. Toxicol. 45: 477–94. doi:10.1146/annurev.pharmtox.45.120403.095821. PMID 15822186.

[urlHuman_Cytochrome_P450_.28CYP.29_Allele_Nomenclature_Committee-4] Sim, Sarah C (2-May-2011). "CYP2C9 allele nomenclature". Cytochrome P450 (CYP) Allele Nomenclature Committee. ^{[self-published source?]}

[pmid16646575-5] García-Martín E, Martínez C, Ladero JM, Agúndez JA (2006). "Interethnic and intraethnic variability of CYP2C8 and CYP2C9 polymorphisms in healthy individuals". Mol Diagn Ther 10 (1): 29–40. doi:10.1007/BF03256440. PMID 16646575.

[pmid18690857-6] Rosemary J, Adithan C (January 2007). "The pharmacogenetics of CYP2C9 and CYP2C19: ethnic variation and clinical significance". Curr Clin Pharmacol 2 (1): 93–109. doi:10.2174/157488407779422302. PMID 18690857.

[pmid9929518-7] Bourrié M, Meunier V, Berger Y, Fabre G (February 1999). "Role of cytochrome P-4502C9 in irbesartan oxidation by human liver microsomes". Drug Metab. Dispos. 27 (2): 288–96. PMID 9929518.

[pmid15049511-8] Salsali M, Holt A, Baker GB (February 2004). "Inhibitory effects of the monoamine oxidase inhibitor tranylcypromine on the cytochrome P450 enzymes CYP2C19, CYP2C9, and CYP2D6". Cell. Mol. Neurobiol. 24 (1): 63–76. doi:10.1023/B:CEMN.0000012725.31108.4a. PMID 15049511.

[pmid11454729-9] Nakajima M, Yoshida R, Shimada N, Yamazaki H, Yokoi T (August 2001). "Inhibition and inactivation of human cytochrome P450 isoforms by phenethyl isothiocyanate". Drug Metab. Dispos. 29 (8): 1110–3. PMID 11454729.

[pmid16645869-10] Zhang JW, Liu Y, Li W, Hao DC, Yang L (July 2006). "Inhibitory effect of medroxyprogesterone acetate on human liver cytochrome P450 enzymes". Eur. J. Clin. Pharmacol. 62 (7): 497–502. doi:10.1007/s00228-006-0128-9. PMID 16645869.

[pmid19074529-11] Si D, Wang Y, Zhou YH, Guo Y, Wang J, Zhou H, Li ZS, Fawcett JP (March 2009). "Mechanism of CYP2C9 inhibition by flavones and flavonols". Drug Metab. Dispos. 37 (3): 629–34. doi:10.1124/dmd.108.023416. PMID 19074529.

[Flockhart-12] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t ^u ^v ^w ^x ^y ^z ^aa ^ab ^ac ^ad ^ae ^af ^ag ^ah ^ai ^aj ^ak ^al ^am ^an ^ao ^ap ^aq ^ar Flockhart DA (2007). "Drug Interactions: Cytochrome P450 Drug Interaction Table". Indiana University School of Medicine.

[FASS-13] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t ^u FASS (drug formulary): "Facts for prescribers (Fakta för förskrivare)". Swedish environmental classification of pharmaceuticals (in Swedish).

[pmid15764711-14] Guo Y, Zhang Y, Wang Y, Chen X, Si D, Zhong D, Fawcett JP, Zhou H (June 2005). "Role of CYP2C9 and its variants (CYP2C9*3 and CYP2C9*13) in the metabolism of lornoxicam in humans". Drug Metab. Dispos. 33 (6): 749–53. doi:10.1124/dmd.105.003616. PMID 15764711.

[Ketoprofen.2C_PubChem-15] ttp://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3825&loc=ec_rcs#x301

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CYP2C9