WordNet

financial assistance in time of need
be beneficial for; "This will do you good" (同)do good
something that aids or promotes well-being; "for the benefit of all" (同)welfare
a performance to raise money for a charitable cause

PrepTutorEJDIC

〈C〉〈U〉ためになること(もの),利益,恩恵 / 〈C〉(国家などにより支払われる)給付金,手当 / 〈U〉慈善興行,募金興行 / …‘の'ためになる,‘に'利益を与える / (…で)利益を得る《from(by)+名》

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/03/12 19:19:24」(JST)

wiki en

Tolvaptan (INN), also known as OPC-41061, is a selective, competitive vasopressin receptor 2 antagonist used to treat hyponatremia (low blood sodium levels) associated with congestive heart failure, cirrhosis, and the syndrome of inappropriate antidiuretic hormone (SIADH). Tolvaptan was approved by the U.S. Food and Drug Administration (FDA) on May 19, 2009, and is sold by Otsuka Pharmaceutical Co. under the trade name Samsca and in India is manufactured & sold by MSN laboratories Ltd. under the trade name Tolsama & Tolvat and by Lupin under the brand name Resodim

Tolvaptan is also in fast-track clinical trials^[2] for polycystic kidney disease. In a 2004 trial, tolvaptan, when administered with traditional diuretics, was noted to increase excretion of excess fluids and improve blood sodium levels in patients with heart failure without producing side effects such as hypotension (low blood pressure) or hypokalemia (decreased blood levels of potassium) and without having an adverse effect on kidney function.^[3] In a recently published trial (TEMPO 3:4 ClinicalTrials.gov number, NCT00428948) the study met its primary and secondary end points. Tolvaptan, when given at an average dose of 95 mg per day over a 3-year period, slowed the usual increase in kidney volume by 50% compared to placebo (2.80% per year versus 5.51% per year, respectively, p<0.001) and reduced the decline in kidney function when compared with that of placebo-treated patients by approximately 30% (reciprocal serum creatinine, -2.61 versus -3.81 (mg/mL)-1 per year, p <0.001)^[4]

Chemistry[edit]

Chemical synthesis:^[5]

Side effects[edit]

FDA has determined that the drug Samsca (tolvaptan) should not be used for longer than 30 days and should not be used in patients with underlying liver disease because it can cause liver injury, potentially leading to liver failure^{[citation needed]}.

References[edit]

^ Shoaf S, Elizari M, Wang Z, et al. (2005). "Tolvaptan administration does not affect steady state amiodarone concentrations in patients with cardiac arrhythmias". J Cardiovasc Pharmacol Ther 10 (3): 165–71. doi:10.1177/107424840501000304. PMID 16211205.
^ Otsuka Maryland Research Institute, Inc.
^ Gheorghiade M, Gattis W, O'Connor C, et al. (2004). "Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial". JAMA 291 (16): 1963–71. doi:10.1001/jama.291.16.1963. PMID 15113814.
^ (2012) Tolvaptan in Patients with Autosomal Dominant Polycystic Kidney Disease
^ Kondo, K.; Ogawa, H.; Yamashita, H.; Miyamoto, H.; Tanaka, M.; Nakaya, K.; Kitano, K.; Yamamura, Y.; Nakamura, S.; Onogawa, T.; et al.; Bioor. Med. Chem. 1999, 7, 1743.

Gheorghiade M, Niazi I, Ouyang J et al. (2003). "Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial". Circulation 107 (21): 2690–6. doi:10.1161/01.CIR.0000070422.41439.04. PMID 12742979.

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. 低ナトリウム血症の治療：抗利尿ホルモン不適合分泌（SIADH）症候群およびreset osmostat症候群treatment of hyponatremia syndrome of inappropriate antidiuretic hormone secretion siadh and reset osmostat [show details]
…oral formulations—tolvaptan, mozavaptan, satavaptan, and lixivaptan—are selective for the V2 receptor, while an intravenous agent, conivaptan, blocks both the V2 and V1a receptors. Tolvaptan should not be …
2. 常染色体優性多発性嚢胞腎の治療treatment of autosomal dominant polycystic kidney disease [show details]
…patients were sequentially administered placebo and tolvaptan to assess their ability to tolerate tolvaptan. Patients who did not tolerate tolvaptan at a dose of 60 mg in the morning and 30 mg in the evening …
3. 心不全患者における低ナトリウム血症hyponatremia in patients with heart failure [show details]
…formulations, including tolvaptan, satavaptan, and lixivaptan, are selective for the V2 receptor, while an intravenous agent, conivaptan, blocks both the V2 and V1a receptors. Only tolvaptan and conivaptan are …
4. 成人における低ナトリウム血症の治療の概要overview of the treatment of hyponatremia in adults [show details]
…formulations, such as tolvaptan, mozavaptan, satavaptan, and lixivaptan, are selective for the V2 receptor, while an intravenous agent, conivaptan, blocks both the V2 and V1a receptors. Only tolvaptan and conivaptan …
5. 肝硬変患者における低ナトリウム血症hyponatremia in patients with cirrhosis [show details]
…impairment). We do not use tolvaptan or other vasopressin receptor antagonists to raise the serum sodium in such patients, although practice varies and some authorities prescribe tolvaptan instead of hypertonic …

English Journal

Utilization and budget impact of tolvaptan in the inpatient setting among patients with heart failure and hyponatremia.

Amin AN1, Ortendahl JD2, Harmon AL2, Kamat SA3, Stellhorn RA3, Chase SL3, Sundar SV3.
Current medical research and opinion.Curr Med Res Opin.2018 Mar;34(3):559-566. doi: 10.1080/03007995.2018.1423958. Epub 2018 Jan 22.
PMID 29297709

Expanding the role of vasopressin antagonism in polycystic kidney diseases: From adults to children?

Janssens P1,2, Weydert C3, De Rechter S3,4, Wissing KM5, Liebau MC6,7,8, Mekahli D3,4.
Pediatric nephrology (Berlin, Germany).Pediatr Nephrol.2018 Mar;33(3):395-408. doi: 10.1007/s00467-017-3672-x. Epub 2017 Apr 28.
PMID 28455745

Rapidity of Correction of Hyponatremia Due to Syndrome of Inappropriate Secretion of Antidiuretic Hormone Following Tolvaptan.

Morris JH1, Bohm NM2, Nemecek BD3, Crawford R4, Kelley D5, Bhasin B6, Nietert PJ7, Velez JCQ8.
American journal of kidney diseases : the official journal of the National Kidney Foundation.Am J Kidney Dis.2018 Feb 22. pii: S0272-6386(18)30004-0. doi: 10.1053/j.ajkd.2017.12.002. [Epub ahead of print]
PMID 29478867

Japanese Journal

心不全における水管理

絹川真太郎,筒井裕之
循環器内科 77(1), 110-116, 2015-01
NAID 40020334905

Effectiveness and Adverse Events of Tolvaptan in Octogenarians With Heart Failure:Interim Analyses of Samsca Post-Marketing Surveillance In Heart faiLurE (SMILE study)

, , , , , ,
International Heart Journal advpub(0), 2015
… The vasopressin receptor 2 (V2) receptor antagonist tolvaptan is an aquaretic agent that has been found to improve symptoms in patients with congestive heart failure. … In this study (SMILE study), we administered tolvaptan to patients aged ≥ 80 years with heart failure accompanied by congestive symptoms and compared its effectiveness and safety profiles in this group with those in patients < …
NAID 130004941352

Vasopressin V2 Receptor Antagonist Tolvaptan Is Effective in Heart Failure Patients With Reduced Left Ventricular Systolic Function and Low Blood Pressure

, , , , , , , , , , , , ,on behalf of the AVCMA investigators
International Heart Journal advpub(0), 2015
… Carperitide has natriuretic and vasodilatory effects, and tolvaptan produces water excretion without electrolyte excretion. … We previously reported the usefulness of tolvaptan compared to carperitide in ADHF patients with fluid volume retention. … The purpose of this study was to examine whether the efficacy of tolvaptan was altered in ADHF patients with reduced left ventricular systolic function and in those with hypotension. …
NAID 130004941350

「benefit」

Tolvaptan
	and enantiomer
Systematic (IUPAC) name
	N-(4-{[(5R)-7-chloro-5-hydroxy-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl]carbonyl}-3-methylphenyl)-2-methylbenzamide
Clinical data
Trade names	Samsca
AHFS/Drugs.com	monograph
MedlinePlus	a609033
Licence data	US FDA:link
Pregnancy cat.	C (US)
Legal status	℞-only (US)
Routes	Oral
Pharmacokinetic data
Bioavailability	Unknown (40% absorbed)
Protein binding	99%
Metabolism	Hepatic (CYP3A4-mediated)
Half-life	12 hours (terminal)
Identifiers
CAS number	150683-30-0
ATC code	C03XA01
PubChem	CID 216237
IUPHAR ligand	2226
ChemSpider	187438
UNII	21G72T1950
ChEMBL	CHEMBL344159
Synonyms	N-{4-[(6R)-9-chloro-6-hydroxy-2-azabicyclo[5.4.0]undeca-8,10,12-triene-2-carbonyl]-3-methyl-phenyl}-2-methyl-benzamide
Chemical data
Formula	C26H25ClN2O3
Mol. mass	448.941 g/mol
	SMILES O=C(c1ccccc1C)Nc2ccc(c(c2)C)C(=O)N4c3ccc(Cl)cc3C(O)CCC4;
	InChI InChI=1S/C26H25ClN2O3/c1-16-6-3-4-7-20(16)25(31)28-19-10-11-21(17(2)14-19)26(32)29-13-5-8-24(30)22-15-18(27)9-12-23(22)29/h3-4,6-7,9-12,14-15,24,30H,5,8,13H2,1-2H3,(H,28,31) ; Key:GYHCTFXIZSNGJT-UHFFFAOYSA-N ;
(what is this?) (verify)