ホシノプリル、フォシノプリル
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出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2013/03/03 12:08:03」(JST)
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Fosinopril
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Systematic (IUPAC) name |
(2S,4S)-4-cyclohexyl-1-(2-{[2-methyl-1-(propanoyloxy)propoxy](4-phenylbutyl)phosphoryl}acetyl)pyrrolidine-2-carboxylic acid |
Clinical data |
Trade names |
Monopril |
AHFS/Drugs.com |
monograph |
MedlinePlus |
a692020 |
Pregnancy cat. |
D (AU) |
Legal status |
℞ Prescription only |
Routes |
oral |
Pharmacokinetic data |
Bioavailability |
~36% |
Protein binding |
87% (fosinoprilat) |
Metabolism |
hepatic, GIT mucosa (to fosinoprilat) |
Half-life |
12 hours (fosinoprilat) |
Excretion |
renal |
Identifiers |
CAS number |
98048-97-6 Y |
ATC code |
C09AA09 |
PubChem |
CID 55891 |
DrugBank |
DB00492 |
ChemSpider |
10482016 Y |
UNII |
R43D2573WO Y |
KEGG |
D07992 Y |
ChEMBL |
CHEMBL1201310 N |
Chemical data |
Formula |
C30H46NO7P |
Mol. mass |
563.663 g/mol |
SMILES
- O=C(CP(=O)(CCCCc1ccccc1)OC(OC(=O)CC)C(C)C)N2C[C@@H](C[C@H]2C(O)=O)C3CCCCC3
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InChI
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InChI=1S/C30H46NO7P/c1-4-28(33)37-30(22(2)3)38-39(36,18-12-11-15-23-13-7-5-8-14-23)21-27(32)31-20-25(19-26(31)29(34)35)24-16-9-6-10-17-24/h5,7-8,13-14,22,24-26,30H,4,6,9-12,15-21H2,1-3H3,(H,34,35)/t25-,26+,30?,39-/m1/s1 Y
Key:BIDNLKIUORFRQP-YYTCENNOSA-N Y
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N (what is this?) (verify)
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Fosinopril is an angiotensin converting enzyme (ACE) inhibitor[1] used for the treatment of hypertension and some types of chronic heart failure. Fosinopril is the only phosphinate-containing ACE inhibitor marketed. It is marketed by Bristol-Myers Squibb under the trade name Monopril.
Fosinoprilat, the active form of fosinopril.
Contents
- 1 Fosinoprilat and Fosinopril
- 2 Congestive heart failure and angiotensin II
- 3 Effects of Fosinopril on treating heart failure
- 4 Benefits of Fosinopril
- 5 References
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Fosinoprilat and Fosinopril
Fosinoprilat proved to have the same problem as enalaprilat and the other carboxylate-containing ACE inhibitors (namely poor oral bioavailability). Addition of a hydrophobic side-chain modulated the ionisation characteristics of the molecule making it more bioavailable. Fosinopril is administered as a prodrug and is converted in vivo to the active form fosinoprilat.
Congestive heart failure and angiotensin II
In congestive heart failure, the ability of the heart to pump enough blood to satisfy the physiological needs of the body is reduced.[2] This condition has a variety of causes, including damaged heart valves, myocardial infarction, hypertension, vitamin B1 deficiency, and genetic mutations. When subsequent blood flow to the kidneys is reduced, the kidneys respond by increasing the secretion of renin from the juxtaglomerular apparatus. Renin converts the inactive angiotensinogen into angiotensin I, which is converted to angiotensin II (AII) by angiotensin converting enzyme (ACE). AII can have negative effects on the cardiovascular system after events such as heart failure and myocardial infarction. AII causes arterial vasoconstriction and hypertension resulting in an increase in afterload, increasing the resistance against which the heart works.[3] Additionally, chronic increase in production of AII is associated with structural changes to the myocardium[4] which reduces the functionality of the heart.[3]
Effects of Fosinopril on treating heart failure
Fosinopril is de-esterified by the liver or gastrointestinal mucosa and is converted to its active form, fosinoprilat.[5] Fosinoprilat competitively binds to ACE, preventing ACE from binding to and converting angiotensin I to angiotensin II. Inhibiting the production of AII lowers peripheral vascular resistance, decreases afterload and decreases blood pressure,[3] thus helping to alleviate the negative effects of AII on cardiac performance. In heart failure patients, fosinopril increases exercise tolerance and lowers the frequency of events associated with worsening heart failure, such as dyspnea, the need for supplemental diuretics, fatigue, and hospitalizations.[6] In a study examining the effects of fosinopril on insulin-like growth factor 1 (IGF-1) and IGF binding protein serum concentrations in high cardiovascular risk patients, a six-month treatment of fosinopril was associated with an elevation in IGF-1.[7] Since a decline in IGF-1 is associated with an increased risk of ischemic heart disease, fosinopril may reduce ischemic risk.
Benefits of Fosinopril
Unlike other ACE inhibitors that are primarily excreted by the kidneys, fosinopril is eliminated from the body via both renal and hepatic pathways.[8] This characteristic of fosinopril makes the drug a safer choice than other ACE inhibitors for heart failure patients with impaired kidney function resulting from poor perfusion[9] as fosinopril can still be eliminated by the liver, preventing accumulation of the drug in the body.[8]
References
- ^ Pilote L, Abrahamowicz M, Eisenberg M, Humphries K, Behlouli H, Tu JV (May 2008). "Effect of different angiotensin-converting-enzyme inhibitors on mortality among elderly patients with congestive heart failure". CMAJ 178 (10): 1303–11. doi:10.1503/cmaj.060068. PMC 2335176. PMID 18458262. http://www.cmaj.ca/cgi/pmidlookup?view=long&pmid=18458262.
- ^ Guyton, Arthur C., Hall, John E. (2006). Textbook of Medical Physiology (11th ed.). Philadelphia: Elsevier Saunders. ISBN 0-7216-0240-1
- ^ a b c Katzung, Bertram G.; Masters, Susan B.; Trevor, Anthony J. (2009). Basic and Clinical Pharmacology. 11th ed. New York: McGraw-Hill. ISBN 978-0-07-160405-5
- ^ Yamagishi H., Kim S., Nishikimi T., Takeuchi K., Takeda T. (1993). Contribution of cardiac renin-angiotensin system to ventricular remodelling in myocardial-infarcted rats. Journal of Molecular and Cellular Cardiology, 25(11):1369-80.
- ^ Duchin K.L., Waclawski A.P., Tu J.I., Manning J., Frantz M., Willard D.A. (1991). Pharmacokinetics, Safety, and Pharmacologic Effects of Fosinopril Sodium, an Angiotensin-Converting Enzyme Inhibitor in Healthy Subjects. Journal of Clinical Pharmacology, 31(1):58-64.
- ^ Erhardt L., MacLean A., Ilgenfritz J., Gelperin K., Blumenthal M. (1995). Fosinopril attenuates clinical deterioration and improves exercise tolerance in patients with heart failure. Fosinopril Efficacy/Safety Trial (FEST) Study Group. European Heart Journal,16(12):1892-9.
- ^ Giovannini S., Cesari M., Marzetti E., Leeuwenburgh C., Maggio M., Pahor M. (2010). Effects of ACE-inhibition on IGF-1 and IGFBP-3 concentrations in older adults with high cardiovascular risk profile. Journal of Nutrition Health and Aging,14(6):457-60.
- ^ a b Zannad F., Chati Z., Guest M., Plat F. (1998). Differential effects of fosinopril and enalapril in patients with mild to moderate chronic heart failure. Fosinopril in Heart Failure Study Investigators. American Heart Journal, 136(4 Pt 1):672-80.
- ^ Greenbaum R., Zucchelli P., Caspi A., Nouriel H., Paz R., Sclarovsky S., O'Grady P., Yee K.F., Liao W.C., Mangold B. (2000). Comparison of the pharmacokinetics of fosinoprilat with enalaprilat and lisinopril in patients with congestive heart failure and chronic renal insufficiency. British Journal of Clinical Pharmacology, 49(1):23-31.
Antihypertensives: agents acting on the renin-angiotensin system (C09)
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ACE inhibitors
("-pril") |
- Sulfhydryl-containing: Captopril
- Zofenopril
- Dicarboxylate-containing: Enalapril#
- Ramipril
- Quinapril
- Perindopril
- Lisinopril (+HCT)
- Benazepril
- Phosphonate-containing: Fosinopril
- Other/ungrouped: Alacepril
- Cilazapril
- Delapril
- Imidapril
- Moexipril
- Rentiapril
- Spirapril
- Temocapril
- Trandolapril
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AIIRAs/
("-sartan") |
- Azilsartan
- Candesartan
- Eprosartan
- Irbesartan
- Losartan (+HCT)
- Olmesartan
- Tasosartan§
- Telmisartan (+HCT)
- Valsartan (+HCT)
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Renin inhibitors/
("-kiren") |
- Aliskiren (+amlodipine)
- Remikiren§
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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anat (a:h/u/t/a/l,v:h/u/t/a/l)/phys/devp/cell/prot
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noco/syva/cong/lyvd/tumr, sysi/epon, injr
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proc, drug (C2s+n/3/4/5/7/8/9)
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UpToDate Contents
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English Journal
- Fast gradient high performance liquid chromatography method with UV detection for simultaneous determination of seven angiotensin converting enzyme inhibitors together with hydrochlorothiazide in pharmaceutical dosage forms and spiked human plasma and urine.
- Elsebaei F, Zhu Y.SourceDepartment of Chemistry, Xixi Campus, Zhejiang University, Hangzhou 310028, China. faelsepai@yahoo.com
- Talanta.Talanta.2011 Jul 15;85(1):123-9. Epub 2011 Mar 30.
- The development of a reversed phase liquid chromatographic method for the simultaneous determination of seven angiotensin converting enzyme (ACE) inhibitors; five drugs namely benazepril HCl (BZL), enalapril maleate (ENL), fosinopril sodium (FSP), lisinopril (LSP) and ramipril (RMP) and two metaboli
- PMID 21645680
- Fosinopril and Losartan Regulate Klotho Gene and Nicotinamide Adenine Dinucleotide Phosphate Oxidase Expression in Kidneys of Spontaneously Hypertensive Rats.
- Tang R, Zhou QL, Ao X, Peng WS, Veeraragoo P, Tang TF.SourceDepartment of Nephrology, Xiangya Hospital, Xiangya Medical College, Central South University, Changsha, China.
- Kidney & blood pressure research.Kidney Blood Press Res.2011 Jun 3;34(5):350-357. [Epub ahead of print]
- Background/Aims: Klotho, a newly identified antiaging gene, predominantly detected in the kidney, has pleiotropic protective effects on kidney diseases. Several studies have confirmed the association between Klotho and oxidative stress. The present studies were performed to explore effects of fosino
- PMID 21646815
Japanese Journal
- Spectrophotometric and Atomic Absorption Determination of Ramipril, Enalapril Maleate and Fosinopril through Ternary Complex Formation with Molybdenum (V)-Thiocyanate (Mo(V)-SCN)
- BARAKA Mohamed Mohamed,EL-SADEK Mohamed,MOUSSA Ewais Moussa Mohamed,ABD-ALATY Nashat Mohamed Alanowar
- Chemical & pharmaceutical bulletin 56(11), 1521-1527, 2008-11-01
- … Three different sensitive and accurate spectroscopic procedures were developed for the determination of three angiotensin-converting enzyme inhibitors, namely, ramipril, enalapril maleate and fosinopril. …
- NAID 110006968051
- Development and validation of liquid chromatography-tandem mass spectrometric method for simultaneous determination of fosinopril and its active metabolite fosinoprilat in human plasma
- CUI Shuangjin,FENG Fang,MA Ming,LIU Han,CHEN Yun
- Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 854(1), 143-151, 2007-07-01
- NAID 10025805129
Related Links
- Fosinopril is an angiotensin converting enzyme (ACE) inhibitor used for the treatment of hypertension and some types of chronic heart failure. Fosinopril is the only phosphinate-containing ACE inhibitor marketed. ...
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