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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/12/26 06:55:18」(JST)
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| Systematic (IUPAC) name | |
|---|---|
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(3R,5R)-7-[2-(4-Fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid
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| Clinical data | |
| Pronunciation | /əˌtɔrvəˈstætən/ |
| Trade names | Lipitor, Atorva |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a600045 |
| Licence data | US Daily Med:link |
| Pregnancy category |
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| Legal status |
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| Routes of administration |
Oral |
| Pharmacokinetic data | |
| Bioavailability | 12% |
| Metabolism | Hepatic - CYP3A4 |
| Biological half-life | 14 h |
| Excretion | Bile |
| Identifiers | |
| CAS Number | 134523-00-5 Y |
| ATC code | C10AA05 |
| PubChem | CID: 60823 |
| IUPHAR/BPS | 2949 |
| DrugBank | APRD00055 N |
| ChemSpider | 54810 Y |
| UNII | A0JWA85V8F N |
| KEGG | D07474 Y |
| ChEBI | CHEBI:39548 Y |
| ChEMBL | CHEMBL1487 Y |
| PDB ligand ID | 117 (PDBe, RCSB PDB) |
| Chemical data | |
| Formula | C33H35FN2O5 |
| Molecular mass | 558.64 |
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SMILES
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InChI
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| NY (what is this?) (verify) | |
Atorvastatin, marketed under the trade name Lipitor among others,[1] is a member of the drug class known as statins, which are used primarily for lowering blood cholesterol and for prevention of events associated with cardiovascular disease. Like all statins, atorvastatin works by inhibiting HMG-CoA reductase, an enzyme found in liver tissue that plays a key role in production of cholesterol in the body.
The synthesis of atorvastatin took place on August 1985 at Warner-Lambert's Parke-Davis Pharmaceutical Research facility in Ann Arbor, Michigan.[2] by Bruce Roth, leading a team of 18 scientists researching atherosclerosis.[3][4][5][3][6][7][4] Although atorvastatin was the fifth drug in the class of statins to be developed, clinical trials showed that atorvastatin caused a more dramatic reduction in LDL-C than the other statin drugs. From 1996 to 2012 under the trade name Lipitor, atorvastatin became the world's best-selling drug of all time, with more than US$125 billion in sales over approximately 14.5 years.[8]
Contents
- 1 Medical uses
- 1.1 Dyslipidemia
- 1.2 Cardiovascular disease
- 1.3 Other uses
- 2 Administration
- 2.1 Specific populations
- 3 Contraindications
- 4 Adverse effects
- 4.1 Major
- 4.2 Common
- 4.3 Other
- 4.4 Interactions
- 5 Mechanism of action
- 6 Pharmacodynamics
- 7 Pharmacokinetics
- 7.1 Absorption
- 7.2 Distribution
- 7.3 Metabolism
- 7.4 Excretion
- 8 Pharmacogenetics
- 9 Chemical synthesis
- 10 History
- 11 Formulations
- 12 Generic availability
- 13 Drug recall
- 14 References
- 15 Further reading
- 16 External links
Medical uses
The primary uses of atorvastatin is for the treatment of dyslipidemia and the prevention of cardiovascular disease:[9]
Dyslipidemia
- Hypercholesterolemia[10] (heterozygous familial and nonfamilial) and mixed dyslipidemia (Fredrickson types IIa and IIb) to reduce total cholesterol, LDL-C,[11] apo-B,[12] triglycerides[13] levels, and CRP[14] as well as increase HDL levels.
- Heterozygous familial hypercholesterolemia[10] in pediatric patients
- Homozygous familial hypercholesterolemia[10][15]
- Hypertriglyceridemia (Fredrickson Type IV)
- Primary dysbetalipoproteinemia (Fredrickson Type III)
- Combined hyperlipidemia[16]
Cardiovascular disease
- Primary prevention of heart attack, stroke, and need for revascularization procedures in patients who have risk factors such as age, smoking, high blood pressure, low HDL-C, and a family history of early heart disease, but have not yet developed clinically evident coronary heart disease.[17]
- Secondary prevention of myocardial infarction, stroke, unstable angina,[18][19] and revascularization in people with established coronary heart disease.[20][21]
- Myocardial infarction and stroke prophylaxis in patients with type II diabetes[22][23][24]
Other uses
There have been recent studies suggesting that high-dose statin therapy plays a plaque-stabilizing role in patients suffering from acute coronary syndrome and thrombotic stroke.[25][26]
Administration
Atorvastatin may be used in combination with bile acid sequestrants and ezetimibe to increase the reduction in cholesterol levels. However, It is not recommended to combine statin drug treatment with certain other cholesterol-lowering drugs, particularly fibrates, because this may increase the risk of myopathy-related adverse effects.[17]
While many statin medications should be administered at bedtime for optimal effect, atorvastatin can be dosed at any time of day, as long as it is continually dosed once daily at the same time.[27][28]
Specific populations
- Geriatric: Plasma concentrations of atorvastatin in healthy elderly subjects are higher than those in young adults, and clinical data suggests a greater degree of LDL-lowering at any dose for patients in the population as compared to young adults.[17]
- Pediatric: Pharmacokinetic data is not available for this population.[17]
- Gender: Plasma concentrations are generally higher in women than in men, but there is no clinically significant difference in the extent of LDL reduction between men and women.[17]
- Renal impairment: Renal disease has no influence on plasma concentrations of atorvastatin and dosing need not be adjusted in these patients.[17]
- Hemodialysis: Hemodialysis will not significantly alter drug levels or change clinical effect of atorvastatin.[17]
- Hepatic impairment: In patients with chronic alcoholic liver disease, levels of atorvastatin may be significantly increased depending upon the extent of liver disease.[17]
Contraindications
- Active liver disease: cholestasis, hepatic encephalopathy, hepatitis, and jaundice
- Unexplained elevations in AST or ALT levels
- Pregnancy: Atorvastatin may cause fetal harm by affecting serum cholesterol and triglyceride levels, which are essential for fetal development.[17]
- Breastfeeding: Small amounts of other statin drugs have been found to pass into breast milk, although atorvastatin has not been studied, specifically.[17]
- Markedly elevated CPK levels or if a myopathy is suspected or diagnosed after dosing of atorvastatin has begun. Very rarely, atorvastatin may cause rhabdomyolysis,[29] and it may be very serious leading to acute renal failure due to myoglobinuria. If rhabdomyolysis is suspected or diagnosed, atorvastatin therapy should be discontinued immediately.[30] The likelihood of developing a myopathy is increased by the co-administration of cyclosporine, fibric acid derivatives, erythromycin, niacin, and azole antifungals.[31]
Adverse effects
Major
- Myopathy with elevation of creatinine kinase (CK)[32] and rhabdomyolysis are the most serious side effects, occurring rarely at a rate of 2.3 to 9.1 per 10,000 person-years among patients taking atorvastatin.[33][16][31] As mentioned previously, atorvastatin should be discontinued immediately if this occurs.
- Persistent liver enzyme abnormalities occurred in 0.7% of patients who received atorvastatin in clinical trials. It is recommended that hepatic function be assessed with laboratory tests before beginning atorvastatin treatment and repeated as clinically indicated thereafter. If evidence of serious liver injury occurs while a patient is taking atorvastatin, it should be discontinued and not restarted until the etiology of the patient's liver dysfunction is defined. If no other cause is found, atorvastatin should be discontinued permanently.[17]
- Diabetes mellitus type 2, an uncommon class effect of all statins.[34][35][36]
Common
The following have been shown to occur in 1–10% of patients taking atorvastatin in clinical trials.
- diarrhea, dyspepsia, nausea[31]
- Arthralgia, myalgia[31]
High-dose atorvastatin have also been associated with worsening glycemic control.[37][38]
Other
In 2014 the FDA reported memory loss, forgetfulness and confusion with all statin products including atorvastatin. The symptoms were not serious, rare and reversible on cessation of drug treatment.[34]
Interactions
Interactions with clofibrate, fenofibrate, gemfibrozil, which are fibrates used in accessory therapy in many forms of hypercholesterolemia, usually in combination with statins, increase the risk of myopathy and rhabdomyolysis.[32][39][40]
Co-administration of atorvastatin with one of CYP3A4 inhibitors such as itraconazole,[41] telithromycin, and voriconazole, may increase serum concentrations of atorvastatin, which may lead to adverse reactions. This is less likely to happen with other CYP3A4 inhibitors such as diltiazem, erythromycin, fluconazole, ketoconazole, clarithromycin, cyclosporine, protease inhibitors, or verapamil,[42] and only rarely with other CYP3A4 inhibitors, such as amiodarone and aprepitant.[30] Often, bosentan, fosphenytoin, and phenytoin, which are CYP3A4 inducers, can decrease the plasma concentrations of atorvastatin. Only rarely, though, barbiturates, carbamazepine, efavirenz, nevirapine, oxcarbazepine, rifampin, and rifamycin,[43] which are also CYP3A4 inducers, can decrease the plasma concentrations of atorvastatin. Oral contraceptives increased AUC values for norethindrone and ethinyl estradiol; these increases should be considered when selecting an oral contraceptive for a woman taking atorvastatin.[44]
Antacids can rarely decrease the plasma concentrations of statin drugs, but do not affect the LDL-C-lowering efficacy.[45]
Niacin also is proved to increase the risk of myopathy or rhabdomyolysis.[30]
Statins may also alter the concentrations of other drugs, such as warfarin or digoxin, leading to alterations in effect or a requirement for clinical monitoring.[30]
Vitamin D supplementation lowers atorvastatin and active metabolite concentrations, yet synergistically reduces LDL and total cholesterol concentrations.[46] Grapefruit juice components are known inhibitors of intestinal CYP3A4.
Co-administration of grapefruit juice with atorvastatin may cause an increase in Cmax and AUC, which can lead to adverse reactions or overdose toxicity.[47]
A few cases of myopathy have been reported when atorvastatin is given with colchicine.[17]
Mechanism of action
Main article: Statin
As with other statins, atorvastatin is a competitive inhibitor of HMG-CoA reductase. Unlike most others, however, it is a completely synthetic compound. HMG-CoA reductase catalyzes the reduction of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) to mevalonate, which is the rate-limiting step in hepatic cholesterol biosynthesis. Inhibition of the enzyme decreases de novo cholesterol synthesis, increasing expression of low-density lipoprotein receptors (LDL receptors) on hepatocytes. This increases LDL uptake by the hepatocytes, decreasing the amount of LDL-cholesterol in the blood. Like other statins, atorvastatin also reduces blood levels of triglycerides and slightly increases levels of HDL-cholesterol.
Recent studies have shown that in patients suffering from acute coronary syndrome, high-dose statin treatment may play a plaque-stabilizing role. At high doses, statins have anti-inflammatory effects, incite reduction of the necrotic plaque core, and improve endothelial function, leading to plaque stabilization and, sometimes, plaque regression. However, there is an increased risk of statin-associated adverse effects with such high-dose statin treatment.[25] There is a similar thought process and risks associated with using high-dose statins to prevent recurrence of thrombotic stroke.[26]
Pharmacodynamics
The liver is the primary site of action of atorvastatin, as this is the principal site of both cholesterol synthesis and LDL clearance. It is the dosage of atorvastatin, rather than systemic drug concentration, which correlates with extent of LDL-C reduction.[17]
Pharmacokinetics
Absorption
Atorvastatin undergoes rapid absorption when taken orally, with an approximate time to maximum plasma concentration (Tmax) of 1–2 h. The absolute bioavailability of the drug is about 14%, but the systemic availability for HMG-CoA reductase activity is approximately 30%. Atorvastatin undergoes high intestinal clearance and first-pass metabolism, which is the main cause for the low systemic availability. Administration of atorvastatin with food produces a 25% reduction in Cmax (rate of absorption) and a 9% reduction in AUC (extent of absorption), although food does not affect the plasma LDL-C-lowering efficacy of atorvastatin. Evening dose administration is known to reduce the Cmax and AUC by 30% each. However, time of administration does not affect the plasma LDL-C-lowering efficacy of atorvastatin.
Distribution
The mean volume of distribution of atorvastatin is approximately 381 L. It is highly protein bound (≥98%), and studies have shown it is likely secreted into human breastmilk.
Metabolism
Atorvastatin metabolism is primarily through cytochrome P450 3A4 hydroxylation to form active ortho- and parahydroxylated metabolites, as well as various beta-oxidation metabolites. The ortho- and parahydroxylated metabolites are responsible for 70% of systemic HMG-CoA reductase activity. The ortho-hydroxy metabolite undergoes further metabolism via glucuronidation. As a substrate for the CYP3A4 isozyme, it has shown susceptibility to inhibitors and inducers of CYP3A4 to produce increased or decreased plasma concentrations, respectively. This interaction was tested in vitro with concurrent administration of erythromycin, a known CYP3A4 isozyme inhibitor, which resulted in increased plasma concentrations of atorvastatin. It is also an inhibitor of cytochrome 3A4.
Excretion
Atorvastatin is primarily eliminated via hepatic biliary excretion, with less than 2% recovered in the urine. Bile elimination follows hepatic and/or extrahepatic metabolism. There does not appear to be any entero-hepatic recirculation. Atorvastatin has an approximate elimination half-life of 14 h. Noteworthy, the HMG-CoA reductase inhibitory activity appears to have a half-life of 20–30 h, which is thought to be due to the active metabolites. Atorvastatin is also a substrate of the intestinal P-glycoprotein efflux transporter, which pumps the drug back into the intestinal lumen during drug absorption.[30]
In hepatic insufficiency, plasma drug concentrations are significantly affected by concurrent liver disease. Patients with A-stage liver disease show a four-fold increase in both Cmax and AUC. Patients with B-stage liver disease show a 16-fold increase in Cmax and an 11-fold increase in AUC.
Geriatric patients (>65 years old) exhibit altered pharmacokinetics of atorvastatin compared to young adults, with mean AUC and Cmax values that are 40% and 30% higher, respectively. Additionally, healthy elderly patients show a greater pharmacodynamic response to atorvastatin at any dose; therefore, this population may have lower effective doses.[31]
Pharmacogenetics
Several genetic polymorphisms have been found to be associated with a higher incidence of undesirable side effects of atorvastatin. This phenomenon is suspected to be related to increased plasma levels of pharmacologically active metabolites, such as atorvastatin lactone and p-hydroxyatorvastatin. Atorvastatin and its active metabolites may be monitored in potentially susceptible patients using specific chromatographic techniques.[48]
Chemical synthesis
Atorvastatin synthesis in commercial production (process) chemistry. The key step of establishing this drug's stereocenters, through initial use of an inexpensive natural product (chiral pool approach).
Atorvastatin synthesis during discovery chemistry. The key step of establishing stereocenters, using of a chiral ester auxiliary approach.
The first synthesis of atorvastatin at Parke-Davis that occurred during drug discovery was racemic followed by chiral chromatographic separation of the enantiomers. An early enantioselective route to atorvastatin made use of an ester chiral auxiliary to set the stereochemistry of the first of the two alcohol functional groups via a diastereoselective aldol reaction.[3][49] Once the compound entered pre-clinical development, process chemistry developed a cost-effective and scalable synthesis.[3] In atorvastatin's case, a key element of the overall synthesis was ensuring stereochemical purity in the final drug substance, and hence establishing the first stereocenter became a key aspect of the overall design. The final commercial production of atorvastatin relied on a chiral pool approach, where the stereochemistry of the first alcohol functional group was carried into the synthesis—through the choice of isoascorbic acid, an inexpensive and easily sourced plant-derived natural product.[3][50]
History
Bruce Roth, who was hired by Warner-Lambert as a young chemist in 1982, had created an "experimental compound" codenamed CI 981 – later called atorvastatin – and moved it "from synthesis in 1985 into expensive clinical trials" when company executives began to balk at the cost.[51][4] Roth's boss Roger Newton and Ronald Cresswell supported the young chemist's costly research but Warner-Lambert was concerned that atorvastatin was a me-too version of rival Merck & Co.'s orphan drug lovastatin (brand name Mevacor). Mevacor, which was first marketed in 1987, was the industry's first statin and Merck's synthetic version – Zocor – was in the advanced stages of development.[51]
In 1994 the findings of a Merck-funded study were published in the The Lancet concluding the efficacy of statins in lowering cholesterol in 4444 Scandinavian patients proving for the first time not only that a "statin reduced “bad” LDL cholesterol but also that it led to a sharp drop in fatal heart attacks among patients with heart disease."[51][52] In 1996 Warner-Lambert entered into a co-marketing agreement with Pfizer to sell Lipitor and in 2000 Pfizer acquired Warner-Lambert 2000 for $90.2 billion.[2][5][3][6] Lipitor was on the market by 1996.[53][7] By 2003 Lipitor had become the best selling pharmaceutical in the United States.[4] From 1996 to 2012 under the trade name Lipitor, atorvastatin became the world's best-selling drug of all time, with more than $125 billion in sales over approximately 14.5 years.[8] Lipitor alone "provided up to a quarter of Pfizer Inc.'s annual revenue for years."[8]
Pfizer's patent on atorvastatin expired in November 2011.[54]
Formulations
Pack and tablet of atorvastatin (Lipitor) 40mg
Atorvastatin calcium tablets are marketed by Pfizer under the trade name Lipitor[55] for oral administration. Tablets are white, elliptical, and film-coated. Pfizer also packages the drug in combination with other drugs, such as with Caduet.[56] Pfizer recommends that patients do not break tablets in half to take half-doses, even when this is recommended by their doctors.
Generic availability
Pfizer's U.S. patent on Lipitor expired on 30 November 2011.[54] Initially, generic atorvastatin was manufactured only by Watson Pharmaceuticals and India's Ranbaxy Laboratories. Prices for the generic version did not drop to the level of other generics—$10 or less for a month's supply—until other manufacturers began to supply the drug in May 2012.[57]
In other countries, atorvastatin calcium is made in tablet form by generic drug makers under various brand names including Stator, Atorvastatin Teva, Litorva, Torid, Atoris, Atorlip, Mactor, Lipvas, Sortis, Torvast, Torvacard, Totalip, and Tulip.[58] Pfizer also makes its own generic version under the name Zarator, which is the sole Pharmac-subsidised brand of atorvastatin in New Zealand.[59]
Drug recall
On 9 November 2012, Indian drugmaker Ranbaxy Laboratories Ltd. voluntarily recalled 10-, 20- and 40-mg doses of its generic version of atorvastatin in the United States. The lots of atorvastatin, packaged in bottles of 90 and 500 tablets, were recalled due to possible contamination with very small glass particles similar to the size of a grain of sand (less than 1 mm in size). The FDA received no reports of injury from the contamination.[60]
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- ^ Mazzu AL, Lasseter KC, Shamblen EC, Agarwal V, Lettieri J, Sundaresen P (October 2000). "Itraconazole alters the pharmacokinetics of atorvastatin to a greater extent than either cerivastatin or pravastatin". Clin. Pharmacol. Ther. 68 (4): 391–400. doi:10.1067/mcp.2000.110537. PMID 11061579.
- ^ Neuvonen PJ, Niemi M, Backman JT (December 2006). "Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance". Clin. Pharmacol. Ther. 80 (6): 565–81. doi:10.1016/j.clpt.2006.09.003. PMID 17178259.
- ^ Backman JT, Luurila H, Neuvonen M, Neuvonen PJ (August 2005). "Rifampin markedly decreases and gemfibrozil increases the plasma concentrations of atorvastatin and its metabolites". Clin. Pharmacol. Ther. 78 (2): 154–67. doi:10.1016/j.clpt.2005.04.007. PMID 16084850.
- ^ "Lipitor". U.S. National Library of Medicine.
- ^ McKenney JM (2005). "Efficacy and safety of rosuvastatin in treatment of dyslipidemia". Am J Health Syst Pharm 62 (10): 1033–47. PMID 15901588.
- ^ Schwartz JB (February 2009). "Effects of vitamin D supplementation in atorvastatin-treated patients: a new drug interaction with an unexpected consequence". Clin. Pharmacol. Ther. 85 (2): 198–203. doi:10.1038/clpt.2008.165. PMID 18754003.
- ^ Kane GC, Lipsky JJ (September 2000). "Drug-grapefruit juice interactions". Mayo Clinic Proceedings 75 (9): 933–42. doi:10.4065/75.9.933. PMID 10994829.
- ^ Deshmukh HA, Colhoun HM, Johnson T, McKeigue PM, Betteridge DJ, Durrington PN, Fuller JH, Livingstone S, Charlton-Menys V, Neil A, Poulter N, Sever P, Shields DC, Stanton AV, Chatterjee A, Hyde C, Calle RA, Demicco DA, Trompet S, Postmus I, Ford I, Jukema JW, Caulfield M, Hitman GA (May 2012). "Genome-wide association study of genetic determinants of LDL-c response to atorvastatin therapy: importance of Lp(a)". J Lipid Res 53 (5): 1000–1011. doi:10.1194/jlr.P021113. PMC 3329377. PMID 22368281.
- ^ Roth BD, Blankley CJ, Chucholowski AW, Ferguson E, Hoefle ML, Ortwine DF, Newton RS, Sekerke CS, Sliskovic DR, Wilson M (1991). "Inhibitors of Cholesterol Biosynthesis. 3. Tetrahydro-4-hydroxy-6-[2-(1H-pyrrol-1-yl)ethyl]-2H-pyran 2-one Inhibitors of HMG-CoA Reductase. 2. Effects of Introducing Substituents at Positions Three and Four of the Pyrrole Nucleus". J. Med. Chem. 34: 357–366. doi:10.1021/jm00105a056. .
- ^ Jie Jack Li, Douglas S. Johnson, Drago R. Sliskovic, Bruce D. Roth (2004). "Chapter 9. Atorvastatin Calcium (Lipitor)". Contemporary Drug Synthesis. John Wiley & Sons, Inc. pp. 113–125. ISBN 0-471-21480-9. .
- ^ a b c Jack, Andrew (28 November 2009). "The fall of the world’s best-selling drug". Financial Times. Retrieved 24 November 2015.
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|access-date=requires|url=(help) - ^ "www.accessdata.fda.gov".
- ^ a b CNN Wire Staff (30 November 2011). "Lipitor loses patent, goes generic". CNN. Retrieved 18 November 2012.
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- ^ News Medical. "Lipitor - What is Lipitor?". Retrieved 3 May 2012.
- ^ "Price to UK for 28 tablets from £3.25 (10mg) to £10.00 (80mg)". National Health Service. June 2012.
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- ^ Rapley, Lisa (31 May 2012). "Atorvastatin sole funding announced". PharmacyToday.co.nz. Retrieved 16 July 2014.
- ^ "FDA Statement on Ranbaxy Atorvastatin Recall". FDA. Retrieved 19 April 2014.
Further reading
- "Highlights of prescribing information" (pdf). Lipitor (atorvastatin calcium) Tablets for oral administration. Pfizer. 2009-06-01. Retrieved 2011-10-26.
- Maggon K (June 2005). "Best-selling human medicines 2002-2004". Drug Discov. Today 10 (11): 739–42. doi:10.1016/S1359-6446(05)03468-9. PMID 15922927.
- Simons J (2003-01-20). "The $10 Billion Pill Hold the fries, please. Lipitor, the cholesterol-lowering drug, has become the bestselling pharmaceutical in history. Here's how Pfizer did it". Fortune. Retrieved 2011-10-26.
- Winslow R (2000-01-24). "The Birth of a Blockbuster: Lipitor's Route out of the Lab". The Wall Street Journal. Retrieved 2011-10-26.
- "Ann Arbor chemist wins national award for drug discovery". ScienceBlog. American Chemical Society. 2003-03-01. Retrieved 2011-10-26.
- Rowe A (2008-08-20). "Meet the Guy Who Invented Lipitor". Wired Science. Wired.com. Retrieved 2011-10-26.
- Bernstein M (2008-08-16). "Chemical Society To Honor 'Heroes Of Chemistry' During National Meeting". Medical News Today. Retrieved 2011-10-26.
- He L (2003-09-27). "Bruce D. Roth, Pfizer Inc, USA". Chinese Academy of Sciences·Institute of Process Engineering. Retrieved 2011-10-26.
External links
- Atorvastatin bound to proteins in the PDB
- Lipitor.com – manufacturer's site
- MedlinePlus Drug information: Atorvastatin (Systemic) – information from USP DI Advice for the Patient
- U.S. National Library of Medicine: Drug Information Portal - Atorvastatin
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UpToDate Contents
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- 1. 心血管疾患または糖尿病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 cardiovascular disease or diabetes
- 2. 急性冠症候群後の低比重リポ蛋白コレステロール（LDL)低下 low density lipoprotein cholesterol ldl c lowering after an acute coronary syndrome
- 3. 心血管疾患の二次予防における脂質低下療法の強度 intensity of lipid lowering therapy in secondary prevention of cardiovascular disease
- 4. スタチン：作用、副作用、および投与 statins actions side effects and administration
- 5. 二次予防における脂質（高コレステロール血症を含む）の治療 treatment of lipids including hypercholesterolemia in secondary prevention
English Journal
- Effects of simvastatin, atorvastatin, ezetimibe, and ezetimibe + simvastatin combination on the inflammatory process and on the liver metabolic changes of arthritic rats.
- Bracht L, Barbosa CP, Caparroz-Assef SM, Cuman RK, Ishii-Iwamoto EL, Bracht A, Bersani-Amado CA.SourceLaboratory of Inflammation, Department of Pharmacy and Pharmacology, University of Maringá, 87.020.900 Maringá, Paraná, Brazil Laboratory of Liver Metabolism, Department of Biochemistry, University of Maringá, Maringá, Brazil.
- Fundamental & clinical pharmacology.Fundam Clin Pharmacol.2012 Dec;26(6):722-34. doi: 10.1111/j.1472-8206.2011.00976.x. Epub 2011 Jul 31.
- In this study, simvastatin, atorvastatin, ezetimibe, and ezetimibe + simvastatin combination were administered to arthritic rats, first to determine their effects on the inflammatory response, employing a low-dose adjuvant-induced arthritis model in rats. Arthritis was induced by the subcutaneou
- PMID 21801201
- CYP7A1 polymorphism influences the LDL cholesterol-lowering response to atorvastatin.
- Jiang XY, Zhang Q, Chen P, Li SY, Zhang NN, Chen XD, Wang GC, Wang HB, Zhuang MQ, Lu M.SourceKey Laboratory for Basic Research in Cardiovascular Science, Ministry of Education, Tongji University School of Medicine, Shanghai Department of Cardiology, Tangshan Gongren Hospital, Hebei Medical University, Tangshan, Hebei province Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
- Journal of clinical pharmacy and therapeutics.J Clin Pharm Ther.2012 Dec;37(6):719-723. doi: 10.1111/j.1365-2710.2012.01372.x. Epub 2012 Aug 8.
- What is known and Objective: Response to the lipid-lowering effect of the statins is known to show significant inter-individual variability. Our aim was to investigate whether genetic variants of the CYP3A5 gene, CYP7A1 gene and ABCG8 gene influence the lipid-lowering response to atorvastatin. Me
- PMID 22882727
Japanese Journal
- リピトール錠からアトルバスタチン錠「EE」に切り替えた際の臨床検査値を指標とした治療学的同等性並びに医療経済的検討
- 大久保 純,池崎 友明,田辺 公一 [他]
- ジェネリック研究 : 日本ジェネリック医薬品学会機関誌 7(2), 116-123, 2013-12
- NAID 40019913786
- 薬剤誘発性帯状ほう疹（スタチンは誘因となりうるか）
- 寺尾 美香,山本 隆之,梅田 二郎,調 裕次
- 皮膚の科学 4(4), 335-338, 2005
- 帯状疱疹は加齢・基礎疾患・薬剤などによる細胞性免疫の低下が発症の誘因となる。一方，近年高脂血症治療薬であるスタチンは免疫抑制作用を持ち合わせていることが認知されている。我々は(1)当院で採用されている362薬剤のうち"帯状疱疹"として副作用報告のあった薬剤，(2)2001年1月から2002年6月まで帯状疱疹で入院していた患者76例の内服薬，(3)スタチン内服中の帯状疱疹患者の合併症，からスタチンが …
- NAID 130004547132
- 多施設共同による錠・カプセル剤の開封性に関する検討
- 大脇 奈保子,間瀬 定政,柴田 ゆうか,牛田 誠,増田 修三,柴田 友紀子,上町 亜希子,小川 克己,熊谷 美香子,横田 学,早川 達
- 医療薬学 30(5), 312-320, 2004-05-10
- … When drugs in the same category and having the same indication were compared, the order of ease of opening was Lochol^[○!R] 20mg, Mevalotin^[○!R] 10mg, Lipovas^[○!R] 5mg and then Lipitor^[○!R] 10mg, and the healthy volunteers found it more difficult to remove Lipovas^[○!R] 5mg from its package than the other 3 HMG-CoA reductase inhibitors. …
- NAID 110001166807
Related Links
- Find information on cholesterol-lowering medication and high cholesterol. Read about the risks and benefits of LIPITOR® (atorvastatin calcium).
- リピトール （Lipitor）. ようこそ！！ ナオルコム へ シッカリ食べて ・・・ バリバリ働き ・・・ グッスリ休んで ・・・ ドッサリうんちをする。 そんな私に・・・・・なりたい。 毒を取り去って アウンの呼吸で 元気に キレイに なりましょう. 「高脂血症薬」「検査」「ベニコウジ」「カ ...
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