関: cerivastatin sodium

同: Baycol

WordNet

an oral drug (trade name Baycol) to reduce blood cholesterol levels (同)Baycol

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/04/19 17:55:21」(JST)

wiki en

Cerivastatin (brand names: Baycol, Lipobay) is a synthetic member of the class of statins used to lower cholesterol and prevent cardiovascular disease. It was marketed by the pharmaceutical company Bayer A.G. in the late 1990s, competing with Pfizer's highly successful atorvastatin (Lipitor). Cerivastatin was voluntarily withdrawn from the market worldwide in 2001, due to reports of fatal rhabdomyolysis.

During postmarketing surveillance, 52 deaths were reported in patients using cerivastatin, mainly from rhabdomyolysis and its resultant renal failure.^[1] Risks were higher in patients using fibrates, mainly gemfibrozil (Lopid), and in patients using the highest (0.8 mg/day) dose of cerivastatin. Bayer A.G. added a contraindication for the concomitant use of cerivastatin and gemfibrozil to the package 18 months after the drug interaction was found.^[2] The frequency of deadly cases of rhabdomyolysis with cerivastatin was 16 to 80 times higher than with other statins.^[3] Another 385 nonfatal cases of rhabdomyolysis were reported. This put the risk of this (rare) complication at 5-10 times that of the other statins. Cerivastatin also induced myopathy in a dose-dependent manner when administered as monotherapy, but that was revealed only after Bayer was sued and unpublished company documents were opened.^[4]

References

^ Furberg CD, Pitt B. Withdrawal of cerivastatin from the world market. Curr Control Trials Cardiovasc Med 2001;2:205-207. PMID 11806796.
^ Psaty BM, Furberg CD, Ray WA, Weiss NS (2004). "Potential for conflict of interest in the evaluation of suspected adverse drug reactions: use of cerivastatin and risk of rhabdomyolysis". JAMA 292 (21): 2622–31. doi:10.1001/jama.292.21.2622. PMID 15572720.
^ Zeitlinger M, Müller M (2003). "[Clinico-pharmacologic explanation models of cerivastatin associated rhabdomyolysis]". Wien Med Wochenschr (in German) 153 (11–12): 250–4. doi:10.1046/j.1563-258X.2003.03029.x. PMID 12879633.
^ Saito M, Hirata-Koizumi M, Miyake S, Hasegawa R (2005). "[Withdrawal of cerivastatin revealed a flaw of post-marketing surveillance system in the United States]". Kokuritsu Iyakuhin Shokuhin Eisei Kenkyusho Hokoku (in Japanese) (123): 41–5. PMID 16541751.

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. スタチン誘発性ミオパチー statin myopathy
2. CTで検出された冠動脈石灰化の診断および予後 diagnostic and prognostic implications of coronary artery calcification detected by computed tomography
3. スタチンと慢性腎臓病 statins and chronic kidney disease
4. 冠動脈疾患患者における脂質低下薬の利益の機序 mechanisms of benefit of lipid lowering drugs in patients with coronary heart disease

English Journal

Application of the extended clearance concept classification system (ECCCS) to predict the victim drug-drug interaction potential of statins.

Kunze A, Poller B, Huwyler J, Camenisch G.
Drug metabolism and personalized therapy.Drug Metabol Personal Ther.2015 May 21. pii: /j/dmdi.ahead-of-print/dmdi-2015-0003/dmdi-2015-0003.xml. doi: 10.1515/dmdi-2015-0003. [Epub ahead of print]
BACKGROUND: During drug development, it is an important safety factor to identify the potential of new molecular entities to become a victim of drug-drug interactions (DDIs). In preclinical development, however, anticipation of clinical DDIs remains challenging due to the lack of in vivo human pharm
PMID 25996489

Quantitative Rationalization of Gemfibrozil Drug Interactions: Consideration of Transporters-Enzyme Interplay and the Role of Circulating Metabolite Gemfibrozil 1-O-β-Glucuronide.

Varma MV1, Lin J2, Bi YA3, Kimoto E3, Rodrigues D2.
Drug metabolism and disposition: the biological fate of chemicals.Drug Metab Dispos.2015 May 4. pii: dmd.115.064303. [Epub ahead of print]
Gemfibrozil has been suggested as a sensitive cytochrome P-450 (CYP)2C8 inhibitor for clinical investigation by the US Food and Drug Administration and the European Medicines Agency. However, gemfibrozil drug-drug interactions (DDIs) are complex as its major circulating metabolite, gemfibrozil 1-O-�
PMID 25941268

A long-standing mystery solved: the formation of 3-hydroxydesloratadine is catalyzed by CYP2C8 but prior glucuronidation of desloratadine by UDP-glucuronosyltransferase 2B10 is an obligatory requirement.

Kazmi F1, Barbara JE2, Yerino P2, Parkinson A2.
Drug metabolism and disposition: the biological fate of chemicals.Drug Metab Dispos.2015 Apr;43(4):523-33. doi: 10.1124/dmd.114.062620. Epub 2015 Jan 16.
Desloratadine (Clarinex), the major active metabolite of loratadine (Claritin), is a nonsedating long-lasting antihistamine that is widely used for the treatment of allergic rhinitis and chronic idiopathic urticaria. For over 20 years, it has remained a mystery as to which enzymes are responsible fo
PMID 25595597

Japanese Journal

スタチンの骨格筋障害に及ぼす酸・アルカリ化誘導剤の影響

小林正紀,日高和宏,知嵜郁美 [他],高橋夏子,小倉次郎,板垣史郎,平野剛,山口浩明,井関健
YAKUGAKU ZASSHI 132(5), 609-615, 2012
… In an in vivo study, plasma creatine phosphokinase (CPK) level was examined in cerivastatin-treated rats. … CHC increased growth inhibition of RD cells induced by cerivastatin, a lipophilic statin, but not these induced by pravastatin, a hydrophilic statin. … On the other hand, citrate suppressed cerivastatin-, simvastatin- and atorvastatin-induced reduction of cell viability and caspase activation in RD cells. …
NAID 130001888677

Cerivastatin induces type-I fiber-, not type-II fiber-, predominant muscular toxicity in the young male F344 rats

Obayashi Hisakuni,Nezu Yoshikazu,Yokota Hatsue [他],KIYOSAWA Naoki,MORI Kazuhiko,MAEDA Naoyuki,TANI Yoshiro,MANABE Sunao,SANBUISSHO Atsushi
Journal of toxicological sciences 36(4), 445-452, 2011-08-01
… To investigate the pathological mechanism of statin-induced myotoxicity, cerivastatin (20 ppm; … Clinical symptoms including weakness of hind limbs, staggering gait and body weight loss, accompanied by marked plasma creatinine kinase elevation in rats fed cerivastatin at around Day 6 to 8. …
NAID 10029340270

糖尿病による血管障害の発症,予防における基礎的検討(特別講演I, 第154回名古屋市立大学医学会例会)

岡山直司
Nagoya medical journal 51(2), 107-114, 2010-09-01
… The enhanced endothelial-neutrophil adhesion and the related adhesion molecule expression induced by high glucose and insulin are significantly inhibited by a sulfonyulurea, gliclazide and some kinds of stains (pravastatin, fluvastatin, and cerivastatin), but not by other sulfonylureas (glibenclamide and glimepiride), nateglinide or a biguanide, metformin. …
NAID 110008147001

Related Pictures

★リンクテーブル★

リンク元	「HMG-CoA還元酵素阻害薬」「セリバスタチン」
拡張検索	「cerivastatin sodium」

「HMG-CoA還元酵素阻害薬」

Cerivastatin
Systematic (IUPAC) name
	(3R,5S,6E)-7-[4-(4-fluorophenyl)-5-(methoxymethyl)-2,6-bis(propan-2-yl)pyridin-3-yl]-3,5-dihydroxyhept-6-enoic acid
Clinical data
Pregnancy; category	AU: D; ;
Legal status
Legal status	Withdrawn from market;
Pharmacokinetic data
Biological half-life	2–3 hours
Identifiers
CAS Number	145599-86-6
ATC code	C10AA06 (WHO)
PubChem	CID 446156
IUPHAR/BPS	2950
DrugBank	DB00439
ChemSpider	393588
UNII	AM91H2KS67
KEGG	D07661
ChEBI	CHEBI:3558
ChEMBL	CHEMBL1477
Chemical data
Formula	C26H34FNO5
Molar mass	459.55 g/mol
	SMILES O=C(O)C[C@H](O)C[C@H](O)/C=C/c1c(nc(c(c1c2ccc(F)cc2)COC)C(C)C)C(C)C ;
	InChI InChI=1S/C26H34FNO5/c1-15(2)25-21(11-10-19(29)12-20(30)13-23(31)32)24(17-6-8-18(27)9-7-17)22(14-33-5)26(28-25)16(3)4/h6-11,15-16,19-20,29-30H,12-14H2,1-5H3,(H,31,32)/b11-10+/t19-,20-/m1/s1 ; Key:SEERZIQQUAZTOL-ANMDKAQQSA-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

「セリバスタチン」

　　[★]

英: cerivastatin、cerivastatin sodium
関: セリバスタチンナトリウム。Baycol

「cerivastatin sodium」

　　[★]

セリバスタチンナトリウム

関: cerivastatin

[1] Furberg CD, Pitt B. Withdrawal of cerivastatin from the world market. Curr Control Trials Cardiovasc Med 2001;2:205-207. PMID 11806796.

[pmid15572720-2] Psaty BM, Furberg CD, Ray WA, Weiss NS (2004). "Potential for conflict of interest in the evaluation of suspected adverse drug reactions: use of cerivastatin and risk of rhabdomyolysis". JAMA 292 (21): 2622–31. doi:10.1001/jama.292.21.2622. PMID 15572720.

[pmid12879633-3] Zeitlinger M, Müller M (2003). "[Clinico-pharmacologic explanation models of cerivastatin associated rhabdomyolysis]". Wien Med Wochenschr (in German) 153 (11–12): 250–4. doi:10.1046/j.1563-258X.2003.03029.x. PMID 12879633.

[pmid16541751-4] Saito M, Hirata-Koizumi M, Miyake S, Hasegawa R (2005). "[Withdrawal of cerivastatin revealed a flaw of post-marketing surveillance system in the United States]". Kokuritsu Iyakuhin Shokuhin Eisei Kenkyusho Hokoku (in Japanese) (123): 41–5. PMID 16541751.

匿名

検索

案内

案内

cerivastatin