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an oral drug (trade name Pravachol) administered to reduce blood cholesterol levels; recommended after nonfatal heart attacks (同)Pravachol

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/12/20 03:23:50」(JST)

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Pravastatin (marketed as Pravachol or Selektine) is a member of the drug class of statins, used in combination with diet, exercise, and weight loss for lowering cholesterol and preventing cardiovascular disease.

Medical uses

Pravastatin is primarily used for the treatment of dyslipidemia and the prevention of cardiovascular disease.^[2] It is recommended to be used only after other measures, such as diet, exercise, and weight reduction, have not improved cholesterol levels.^[2]

The evidence for the use of pravastatin is generally weaker than for other statins. The antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT), failed to demonstrate a difference in all-cause mortality or nonfatal myocardial infarction/fatal coronary heart disease rates between patients receiving pravastatin 40 mg daily (a common starting dose) and those receiving usual care.^[3]

Adverse effects and contraindications

Pravastatin has undergone over 112,000 patient-years of double-blind, randomized trials using the 40-mg, once-daily dose and placebos. These trials indicate pravastatin is well tolerated and displays few noncardiovascular abnormalities in patients.^[4] However, side effects may occur. A doctor should be consulted if symptoms such as heartburn or headache are severe and do not go away.

These uncommon side effects should be promptly reported to the prescribing doctor or an emergency medical service:^[2]

muscle pain, tenderness, or weakness
lack of energy
fever
jaundice, yellowing of the skin or eyes
pain in the upper right part of the stomach
nausea
extreme tiredness
unusual bleeding or bruising
dark-colored urine
loss of appetite
flu-like symptoms
rash
hives
itching
difficulty breathing or swallowing
swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
hoarseness

These symptoms should be reported to the prescribing doctor if they persist or increase in severity:

heartburn
headache
memory loss or forgetfulness
confusion

Contraindications, conditions that warrant withholding treatment with pravastatin, include pregnancy and breastfeeding.^[5] Taking pravastatin while pregnant could lead to birth defects. While the amount of pravastatin ingested by an infant from breastfeeding is low, patients breastfeeding should not take pravastatin due to potential effects on the infant's lipid metabolism.^[6]

Drug interactions

Medications that should not be taken with pravastatin include, but are not limited to:^[2]^[5]

Cimetidine (Tagamet)
Colchicine (Colcrys)
Cyclosporine (Neoral, Sandimmune)
Ketoconazole (Nizoral)
Additional cholesterol-lowering medications such as: fenofibrate (Tricor), gemfibrozil (Lopid), cholestyramine (Questran, Questran Light, Cholybar), and niacin (nicotinic acid, Niacor, Niaspan);
Specific HIV protease inhibitors such as: lopinavir and ritonavir (Kaletra), and ritonavir (Norvir) taken with darunavir (Prezista); and spironolactone (Aldactone).

Pravastatin is cleared by the kidney, giving it a distinct advantage over other statins when a potential for drug interactions using the hepatic pathway exists.

Mechanism of action

Pravastatin acts as a lipoprotein-lowering drug through two pathways. In the major pathway, pravastatin inhibits the function of hydroxymethylglutaryl-CoA (HMG-CoA) reductase. As a reversible competitive inhibitor, pravastatin sterically hinders the action of HMG-CoA reductase by occupying the active site of the enzyme. Taking place primarily in the liver, this enzyme is responsible for the conversion of HMG-CoA to mevalonate in the rate-limiting step of the biosynthetic pathway for cholesterol. Pravastatin also inhibits the synthesis of very-low-density lipoproteins, which are the precursor to low-density lipoproteins (LDL). These reductions increase the number of cellular LDL receptors, thus LDL uptake increases, removing it from the bloodstream.^[7] Overall, the result is a reduction in circulating cholesterol and LDL. A minor reduction in triglycerides and an increase in high-density lipoproteins (HDL) are common.

History

Initially known as CS-514, pravastatin is a derivative of ML236B (compactin), which was identified in a fungus called Penicillium citrinum in the 1970s by researchers of the Sankyo Pharma Inc.^[8] It is being marketed outside Japan by the pharmaceutical company Bristol-Myers Squibb. In 2005, Pravachol was the 22nd-highest selling brand-name drug in the United States, with sales totaling $1.3 billion.^[9]

The U.S. Food and Drug Administration approved generic pravastatin for sale in the United States for the first time on April 24, 2006. Generic pravastatin sodium tablets are manufactured by Biocon Ltd, India and TEVA Pharmaceuticals in Kfar Sava, Israel.^[9]

References

^ ^a ^b ^c ^d Neuvonen, PJ; Backman, JT; Niemi, M (2008). "Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin.". Clinical Pharmacokinetics 47 (7): 463–74. doi:10.2165/00003088-200847070-00003. PMID 18563955.
^ ^a ^b ^c ^d "Prevachol". The American Society of Health-System Pharmacists. Retrieved 3 April 2011. Cite error: Invalid <ref> tag; name "AHFS" defined multiple times with different content (see the help page).
^ No Authors Listed (2002). "Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT)". JAMA 288 (23): 2998–3007. doi:10.1001/jama.288.23.2998. PMID 12479764.
^ Pfeffer MA, Keech A, Sacks FM, et al. "Safety and tolerability of pravastatin in long-term clinical trials: prospective Pravastatin Pooling (PPP) Project." Circulation 2002;105:2341-2346
^ ^a ^b Williams, Eni. "Pravachol Side Effects Center". RxList. Retrieved 1 December 2012.
^ "Pravastatin". LactMed. U.S. National Library of Medicine. Retrieved 1 December 2012.
^ Vaughan, C. J., and A. M. Gotto, Jr. 2004. Update on statins: 2003. Circulation 110: 886–892.
^ Jonathan A. Tobert Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors Nature Reviews Drug Discovery 2, 517-526 (July 2003) PMID 12815379
^ ^a ^b "FDA Approves First Generic Pravastatin". Retrieved 2008-01-20.

External links

Pravachol information from the National Institute of Health
Package insert for Pravachol

UpToDate Contents

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1. 冠動脈疾患または同等の冠動脈リスクを有する患者におけるコレステロール低下に関する
臨床試験 clinical trials of cholesterol lowering in patients with coronary heart disease or coronary risk equivalents
2. スタチン：作用、副作用、および投与 statins actions side effects and administration
3. 小児の脂質異常症ののマネージメント management of pediatric dyslipidemia
4. スタチン誘発性ミオパチー statin myopathy
5. スタチンと慢性腎臓病 statins and chronic kidney disease

English Journal

Effect of preoperative oral pravastatin reload in systemic inflammatory response and myocardial damage after coronary artery bypass grafting. A pilot double-blind placebo-controlled study.

Castaño M1, González-Santos JM, López J, García B, Centeno JE, Aparicio B, Bueno MJ, Díez R, Sagredo V, Rodríguez J, García-Criado FJ.
The Journal of cardiovascular surgery.J Cardiovasc Surg (Torino).2015 Aug;56(4):617-29.
AIM: Statins exert pleiotropic effects that result in cardioprotective and antiinflammatory properties. There is a lack of information about the effect of preoperative reloading statin administration in surgical coronary patients regarding myocardial protection, systemic inflammatory response (SIR)
PMID 25968407

Idarubicin, cytarabine, and pravastatin as induction therapy for untreated acute myeloid leukemia and high-risk myelodysplastic syndrome.

Shadman M1,2, Mawad R3, Dean C1, Chen TL4, Shannon-Dorcy K1, Sandhu V1, Hendrie PC5, Scott BL1,2, Walter RB1,5, Becker PS1,5, Pagel JM3, Estey EH1,5.
American journal of hematology.Am J Hematol.2015 Jun;90(6):483-6. doi: 10.1002/ajh.23981. Epub 2015 Feb 27.
Previous studies suggest that idarubicin/cytarabine(ara-C)/pravastatin (IAP) is an active salvage regimen for patients with AML. We therefore investigated this regimen in patients with newly-diagnosed AML or MDS (≥10% blasts). Patients were eligible if the anticipated treatment-related mortality (
PMID 25689471

Early initiation of statin treatment in children with familial hypercholesterolaemia.

Braamskamp MJ1, Hutten BA, Wiegman A.
Current opinion in lipidology.Curr Opin Lipidol.2015 Jun;26(3):236-9. doi: 10.1097/MOL.0000000000000177.
PURPOSE OF REVIEW: This article provides recent insights on the early onset of atherosclerosis in heterozygous familial hypercholesterolemia and reports on novel treatment options as well as on the consequences of long-term statin use in childhood.RECENT FINDINGS: Children with familial hypercholest
PMID 25943840

Japanese Journal

プラバスタチンはplacental growth factor(PGF)を誘導し,妊娠高血圧症候群モデルマウスの症状を軽減する(優秀論文賞受賞講演,第64回日本産科婦人科学会・学術講演会)

熊澤惠一
日本産科婦人科學會雜誌 64(8), 1865-1875, 2012-08-01
NAID 110009489649

Ezetimibe Improves Endothelial Function and Inhibits Rho-Kinase Activity Associated With Inhibition of Cholesterol Absorption in Humans

NOCHIOKA Kotaro,TANAKA Shin-ichi,MIURA Masanobu,ZHULANQIQIGE Do. e,FUKUMOTO Yoshihiro,SHIBA Nobuyuki,SHIMOKAWA Hiroaki
Circulation journal : official journal of the Japanese Circulation Society 76(8), 2023-2030, 2012-07-25
… mean age, 31±3 [SD] years-old) were randomized to receive ezetimibe (10mg/day) or pravastatin (10mg/day) for 4 weeks in a cross-over manner with a 4-week washout interval. … Although ezetimibe and pravastatin equally reduced low-density lipoprotein cholesterol (E: -25% vs. P: -21%), the CLR was reduced by ezetimibe but was rather increased by pravastatin (E: -41% vs. P: +37%; … Reduction in RLP-C by ezetimibe was greater compared with pravastatin (E: -33% vs. P: -14%; …
NAID 10030505144

Related Pictures

★リンクテーブル★

リンク元	「HMG-CoA還元酵素阻害薬」「プラバスタチン」
拡張検索	「pravastatin sodium」

「HMG-CoA還元酵素阻害薬」

Pravastatin
Systematic (IUPAC) name
	(3R,5R)-3,5-dihydroxy-7-((1R,2S,6S,8R,8aR)-6-hydroxy-2-methyl-8-{[(2S)-2-methylbutanoyl]oxy}-1,2,6,7,8,8a-hexahydronaphthalen-1-yl)-heptanoic acid
Clinical data
Trade names	Pravachol
AHFS/Drugs.com	monograph
MedlinePlus	a692025
Pregnancy; category	AU: D; US: X (Contraindicated); ;
Legal status	AU: S4 (Prescription only); CA: ℞-only; UK: POM (Prescription only); US: ℞-only;
Routes of; administration	oral
Pharmacokinetic data
Bioavailability	18%
Protein binding	50%
Metabolism	Hepatic (minimal)
Biological half-life	1-3 hours
Identifiers
CAS Number	81093-37-0
ATC code	C10AA03
PubChem	CID: 54687
IUPHAR/BPS	2953
DrugBank	DB00175
ChemSpider	49398
UNII	KXO2KT9N0G
ChEBI	CHEBI:63618
ChEMBL	CHEMBL1144
Chemical data
Formula	C23H36O7
Molecular mass	424.528 g/mol
	SMILES O=C(O)C[C@H](O)C[C@H](O)CC[C@H]2[C@H](/C=C\C1=C\[C@@H](O)C[C@H](OC(=O)[C@@H](C)CC)[C@@H]12)C ;
	InChI InChI=1S/C23H36O7/c1-4-13(2)23(29)30-20-11-17(25)9-15-6-5-14(3)19(22(15)20)8-7-16(24)10-18(26)12-21(27)28/h5-6,9,13-14,16-20,22,24-26H,4,7-8,10-12H2,1-3H3,(H,27,28)/t13-,14-,16+,17+,18+,19-,20-,22-/m0/s1 ; Key:TUZYXOIXSAXUGO-PZAWKZKUSA-N ;
(what is this?) (verify)

　　[★]

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

「プラバスタチン」

　　[★]

英: pravastatin
化: プラバスタチンナトリウム pravastatin sodium
商: アルセチン、コレリット、タツプラミン、プラバスタン、プラバチン、プラバピーク、プラバメイト、プラメバン、プロバチン、マイバスタン、メバトルテ、メバリッチ、メバリリン、メバレクト、メバロチン、メバン、リダックM
関: HMG-CoA還元酵素阻害薬; 高脂血症用剤

「pravastatin sodium」

　　[★]

プラバスタチンナトリウム

関: pravastatin

[PK-1] Neuvonen, PJ; Backman, JT; Niemi, M (2008). "Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin.". Clinical Pharmacokinetics 47 (7): 463–74. doi:10.2165/00003088-200847070-00003. PMID 18563955.

[AHFS-2] "Prevachol". The American Society of Health-System Pharmacists. Retrieved 3 April 2011. Cite error: Invalid <ref> tag; name "AHFS" defined multiple times with different content (see the help page).

[3] No Authors Listed (2002). "Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT)". JAMA 288 (23): 2998–3007. doi:10.1001/jama.288.23.2998. PMID 12479764.

[4] Pfeffer MA, Keech A, Sacks FM, et al. "Safety and tolerability of pravastatin in long-term clinical trials: prospective Pravastatin Pooling (PPP) Project." Circulation 2002;105:2341-2346

[RxList-5] Williams, Eni. "Pravachol Side Effects Center". RxList. Retrieved 1 December 2012.

[LactMed-6] "Pravastatin". LactMed. U.S. National Library of Medicine. Retrieved 1 December 2012.

[7] Vaughan, C. J., and A. M. Gotto, Jr. 2004. Update on statins: 2003. Circulation 110: 886–892.

[Tolbert-8] Jonathan A. Tobert Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors Nature Reviews Drug Discovery 2, 517-526 (July 2003) PMID 12815379

[fda_announcement-9] "FDA Approves First Generic Pravastatin". Retrieved 2008-01-20.

匿名

検索

案内

案内

pravastatin