TOLVAPTAN

Details

Stereochemistry	RACEMIC
Molecular Formula	C26H25ClN2O3
Molecular Weight	448.941
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=CC=CC=C1C(=O)NC2=CC(C)=C(C=C2)C(=O)N3CCCC(O)C4=C3C=CC(Cl)=C4

InChI

InChIKey=GYHCTFXIZSNGJT-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB06212
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/samsca.html

Tolvaptan is a selective and competitive arginine vasopressin receptor 2 antagonist. Vasopressin acts on the V2 receptors found in the walls of the vasculature and luminal membranes of renal collecting ducts. By blocking V2 receptors in the renal collecting ducts, aquaporins do not insert themselves into the walls thus preventing water absorption. This action ultimately results in an increase in urine volume, decrease urine osmolality, and increase electrolyte-free water clearance to reduce intravascular volume and an increase serum sodium levels. Tolvaptan is especially useful for heart failure patients as they have higher serum levels of vasopressin. Tolvaptan is used to treat low blood sodium levels (hyponatremia) associated with various conditions like congestive heart failure, cirrhosis, and syndrome of inappropriate antidiuretic hormones (SIADH). FDA approved on May 19, 2009. Tolvaptan is sold under the trade names Samsca and Jinarc.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Vasopressin V2 receptor 15 Target ID: CHEMBL1790 Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=5526617c-c7b9-4556-886d-729bbabbc566&type=display	Antagonist 2778		0.43 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypervolemic and euvolemic hyponatremia 1 Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=5526617c-c7b9-4556-886d-729bbabbc566&type=display	Primary		Approved 8429	Samsca Approved Use Samsca® is indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia (serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction), including patients with heart failure and Syndrome of Inappropriate Antidiuretic Hormone (SIADH). Launch Date 2009

C_max

Value	Dose	Analyte	Population
198 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22120090	30 mg 1 times / day multiple, oral dose: 30 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TOLVAPTAN blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
125 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22120090	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLVAPTAN blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
154 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22120090	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLVAPTAN blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

AUC

Value	Dose	Analyte	Population
1193 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22120090	30 mg 1 times / day multiple, oral dose: 30 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TOLVAPTAN blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
683 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22120090	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLVAPTAN blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
719 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22120090	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLVAPTAN blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

T_1/2

Value	Dose	Analyte	Population
3.3 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22120090	30 mg 1 times / day multiple, oral dose: 30 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TOLVAPTAN blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3.5 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22120090	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLVAPTAN blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3.2 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22120090	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLVAPTAN blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

Doses

Dose	Population	Adverse events
480 mg single, oral Highest studied dose Dose: 480 mg Route: oral Route: single Dose: 480 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17925589	healthy, 32 years (range: 20-51 years) n = 6 Health Status: healthy Age Group: 32 years (range: 20-51 years) Sex: M+F Population Size: 6 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17925589	Other AEs: Thirst, Urinary frequency... Other AEs: Thirst (6 patients) Urinary frequency (6 patients) Dry mouth (2 patients) Headache NOS (2 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17925589
96 mg 1 times / day steady, oral (mean) Dose: 96 mg, 1 times / day Route: oral Route: steady Dose: 96 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf	unhealthy, 39 years n = 961 Health Status: unhealthy Condition: autosomal dominant polycystic kidney disease Age Group: 39 years Sex: M+F Population Size: 961 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf	Disc. AE: Pollakiuria, Polyuria... AEs leading to discontinuation/dose reduction: Pollakiuria (6.6%) Polyuria (6.6%) Nocturia (6.6%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf
300 mg 1 times / day multiple, oral Highest studied dose Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf	healthy, adult Health Status: healthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf
1 mg single, intravenous Dose: 1 mg Route: intravenous Route: single Dose: 1 mg Sources: https://pubmed.ncbi.nlm.nih.gov/22257581	healthy, adult n = 14 Health Status: healthy Age Group: adult Population Size: 14 Sources: https://pubmed.ncbi.nlm.nih.gov/22257581	Sources: https://pubmed.ncbi.nlm.nih.gov/22257581
60 mg 1 times / day steady, oral (total) Recommended Dose: 60 mg, 1 times / day Route: oral Route: steady Dose: 60 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf	unhealthy Health Status: unhealthy Condition: autosomal dominant polycystic kidney disease Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf	Other AEs: Liver injury... Other AEs: Liver injury (serious) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf

AEs

AE	Significance	Dose	Population
Dry mouth	2 patients	480 mg single, oral Highest studied dose Dose: 480 mg Route: oral Route: single Dose: 480 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17925589	healthy, 32 years (range: 20-51 years) n = 6 Health Status: healthy Age Group: 32 years (range: 20-51 years) Sex: M+F Population Size: 6 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17925589
Headache NOS	2 patients	480 mg single, oral Highest studied dose Dose: 480 mg Route: oral Route: single Dose: 480 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17925589	healthy, 32 years (range: 20-51 years) n = 6 Health Status: healthy Age Group: 32 years (range: 20-51 years) Sex: M+F Population Size: 6 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17925589
Thirst	6 patients	480 mg single, oral Highest studied dose Dose: 480 mg Route: oral Route: single Dose: 480 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17925589	healthy, 32 years (range: 20-51 years) n = 6 Health Status: healthy Age Group: 32 years (range: 20-51 years) Sex: M+F Population Size: 6 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17925589
Urinary frequency	6 patients	480 mg single, oral Highest studied dose Dose: 480 mg Route: oral Route: single Dose: 480 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17925589	healthy, 32 years (range: 20-51 years) n = 6 Health Status: healthy Age Group: 32 years (range: 20-51 years) Sex: M+F Population Size: 6 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf https://pubmed.ncbi.nlm.nih.gov/17925589
Nocturia	6.6% Disc. AE	96 mg 1 times / day steady, oral (mean) Dose: 96 mg, 1 times / day Route: oral Route: steady Dose: 96 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf	unhealthy, 39 years n = 961 Health Status: unhealthy Condition: autosomal dominant polycystic kidney disease Age Group: 39 years Sex: M+F Population Size: 961 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf
Pollakiuria	6.6% Disc. AE	96 mg 1 times / day steady, oral (mean) Dose: 96 mg, 1 times / day Route: oral Route: steady Dose: 96 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf	unhealthy, 39 years n = 961 Health Status: unhealthy Condition: autosomal dominant polycystic kidney disease Age Group: 39 years Sex: M+F Population Size: 961 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf
Polyuria	6.6% Disc. AE	96 mg 1 times / day steady, oral (mean) Dose: 96 mg, 1 times / day Route: oral Route: steady Dose: 96 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf	unhealthy, 39 years n = 961 Health Status: unhealthy Condition: autosomal dominant polycystic kidney disease Age Group: 39 years Sex: M+F Population Size: 961 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf
Liver injury	serious	60 mg 1 times / day steady, oral (total) Recommended Dose: 60 mg, 1 times / day Route: oral Route: steady Dose: 60 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf	unhealthy Health Status: unhealthy Condition: autosomal dominant polycystic kidney disease Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/204441lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 699 NTCP 34 BSEP 402 MATE1 306 MATE2 263 MRP2 383 MRP3 157 MRP4 204 OAT1 599 OAT3 642 OATP1B1 788 OATP1B3 706 OCT1 512 OCT2 647 P-gp 1461	P-gp 1537

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=5 Page: 6.0	yes [IC50 0.837 uM]
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=6 Page: 6,11	yes [IC50 15.9 uM]	weak (co-administration study) Comment: administration with digoxin increased Digoxin Cmax and AUC by 30% and 20%, respectively Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=6 Page: 6,11
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	yes [IC50 27.2 uM]
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=5 Page: 6.0	yes [IC50 4.14 uM]
NTCP 35	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=16 Page: 16.0	yes [IC50 41.5 uM]
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=5 Page: 6.0	yes [IC50 5.47 uM]
MRP2 475	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=5 Page: 6.0	yes [IC50 50 uM]
MRP3 207	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=5 Page: 6.0	yes [IC50 50 uM]
MRP4 238	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=5 Page: 6.0	yes [IC50 50 uM]
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=5 Page: 6.0	yes [IC50 6.15 uM]
MATE1 308	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=5 Page: 6.0	yes [IC50 7.965 uM]
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=6 Page: 6,11	yes [IC50 8.32 uM]
MATE2 263	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=5 Page: 6.0	yes [IC50 >10 uM]
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=5 Page: 6.0	yes [IC50 >30 uM]
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=5 Page: 6.0	yes [Ki 34 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	yes
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=96 Page: 96.0	yes		yes (co-administration study) Comment: administration with ketoconazole caused a 3.5-fold and 5-fold increase in tolvaptan Cmax and AUC, respectively; administration with rifmapin reduced Cmax and AUC of tolvaptan to 10 and 20%, respectively; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/204441Orig1s000ClinPharmR.pdf#page=96 Page: 96.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022275s000_PharmR_P1.pdf#page=31 Page: 31.0

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY526018	https://www.001chemical.com/chem/150683-30-0
AEchem Scientific Corp., USA	AE1-013459	http://www.aechemsc.com/info_products/AE1-013459.php
AK Scientific, Inc. (AKSCI)	66720	http://www.aksci.com/item_detail.php?cat=66720
Achemtek	0102-014531	http://www.achemtek.com/150683-30-0
Acorn PharmaTech	ACN-040195	http://www.acornpharmatech.com/
Alsachim	2932	http://www.alsachim.com/product-C4002-glo.bal-view.html
Ambinter	Amb17620728	http://www.ambinter.com/reference/17620728
Anward	ANW-59865	http://www.anward.com/pro_result/46316
Ark Pharm	AK-33401	http://www.arkpharminc.com/products/150683-30-0.html
AstaTech, Inc.	40033	http://www.astatechinc.com/CPSResult.php?CRNO=39143
Aurora Fine Chemicals LLC	A13.108.065	http://online.aurorafinechemicals.com/info?ID=A13.108.065
AvaChem Scientific	2634	http://www.avachem.com/productSearch.asp?2634
Axon MedChem	1591	https://www.axonmedchem.com/product/1591
BOC Sciences	1246818-18-7	https://www.bocsci.com/tolvaptan-d7-cas-1246818-18-7-item-484313.html
Boerchem	BC650606	http://www.boerchem.com/?product_38814.html
Chem Scene	CS-0572	http://www.chemscene.com/150683-30-0.html
ChemMol	30115910	http://www.chemmol.com/chemmol/30115910.html
ChemMol	44012557	http://www.chemmol.com/chemmol/44012557.html
ChemMol	49400063	http://www.chemmol.com/chemmol/49400063.html
ChemWise	AR60127	http://www.chemwisellc.com/product/tolvaptan-2/
ChemWise	AR60125	http://www.chemwisellc.com/product/tolvaptan/
Chemspace	CSSB00016987605	https://chem-space.com/CSSB00016987605
Clearsynth	CS-O-02900	https://www.clearsynth.com/en/CSO02900.html
Clearsynth	CS-O-31027	https://www.clearsynth.com/en/CSO31027.html
Clearsynth	CS-T-44605	https://www.clearsynth.com/en/CST44605.html
DC Chemicals	DC9148	http://www.dcchemicals.com/product_show-Tolvaptan.html
Finetech	FT-0675288	http://www.finetechnology-ind.com/prod/detail/pub/331947-44-5.html
Finetech	FT-0675287	http://www.finetechnology-ind.com/prod/detail/pub/331947-66-1.html
Hairui	HR120724	http://www.hairuichem.com/en/product/150683-30-0.html
Hefei Hirisun Pharmatech Co., Ltd	HR130551	http://www.hirisunpharm.com/150683-30-0.html
Hello Bio	HB2651	http://www.hellobio.com/4-methylhistamine-dihydrochloride.html
LGC Standards	MM3561.00	https://www.lgcstandards.com/US/en/p/MM3561.00
Lab Network	LN00196860	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00196860
Matrix Scientific	94534	https://www.matrixscientific.com/094534.html
MedChem Express	HY-17000	https://www.medchemexpress.com/Tolvaptan.html
MolPort	MolPort-008-155-996	https://www.molport.com/shop/molecule-link/MolPort-008-155-996
Molcore	MC526018	https://www.molcore.com/product/150683-30-0
OChem	24490	http://www.ocheminc.com/index.php?act=psearch&pid=683T300
Oakwood	361970	http://www.oakwoodchemical.com/ProductsList.aspx?CategoryID=-2&txtSearch=150823&ExtHyperLink=1
Shanghai Send Pharmaceutical Technology Co., Ltd	send21416	http://shsendpharm.com/
Sigma-Aldrich	T7455_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/t7455?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sun-shine Chemical	Tolvaptan	http://www.sun-shinechem.com/Details/Tolvaptan/2010/150683-30-0.html
Tocris	5181	https://www.tocris.com/products/tolvaptan_5181
TripleBond	CT0200	http://www.triplebond-canada.com/prod/1632/
Yuhao Chemical	RT9638	http://www.chemyuhao.com/150683-30-0.html
abcr GmbH	AB358162	http://www.abcr.com/shop/en/AB358162
eNovation Chemicals	D142062	https://www.enovationchem.com/ProductDetails.asp?ProductID=D142062
iChemical	EBD30732	http://www.ichemical.com/products/150683-30-0.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
Comparison of 60-day mortality in hospitalized heart failure patients with versus without hypothermia.	2006 Dec 1	17126655
Vasopressin antagonists as aquaretic agents for the treatment of hyponatremia.	2006 Jul	16843091
Vasopressin antagonists--progress and promise.	2006 Nov 16	17105758
Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia.	2006 Nov 16	17105757
Gateways to clinical trials.	2006 Sep	17003851
AVP receptor antagonists as aquaretics: review and assessment of clinical data.	2006 Sep	16970150
Improvement in hyponatremia during hospitalization for worsening heart failure is associated with improved outcomes: insights from the Acute and Chronic Therapeutic Impact of a Vasopressin Antagonist in Chronic Heart Failure (ACTIV in CHF) trial.	2007	17573581
Aquaretic agents: what's beyond the treatment of hyponatremia?	2007	17430186
Therapeutic potential of vasopressin receptor antagonists.	2007	17428103
Cerebral correlates of hyponatremia.	2007	17356196
[Vasopressin antagonists in treatment of hyponatremia].	2007 Aug	18018383
Pharmacokinetic and pharmacodynamic interaction between tolvaptan, a non-peptide AVP antagonist, and furosemide or hydrochlorothiazide.	2007 Aug	17703139
Effects of tolvaptan, an oral vasopressin V2 receptor antagonist, in hyponatremia.	2007 Aug	17660019
Tolvaptan, an oral vasopressin V2 receptor antagonist for heart failure?	2007 Dec	18037090
Clinical trials update from the European Society of Cardiology Congress in Vienna, 2007: PROSPECT, EVEREST, ARISE, ALOFT, FINESSE, Prague-8, CARESS in MI and ACUITY.	2007 Dec	17992567
Pharmacokinetics, pharmacodynamics, and safety of tolvaptan, a nonpeptide AVP antagonist, during ascending single-dose studies in healthy subjects.	2007 Dec	17925589
Diagnosis and management of hyponatremia in cancer patients.	2007 Dec	17701059
Aminocarbonylation route to tolvaptan.	2007 Dec 1	17933527
Recognition and treatment of hyponatremia in acutely ill hospitalized patients.	2007 Feb	17472815
Evaluation and management of hyponatremia: an emerging role for vasopressin receptor antagonists.	2007 Feb	17251996
Nephrogenic syndrome of inappropriate antidiuresis in adults: high phenotypic variability in men and women from a large pedigree.	2007 Feb	17229917
New agents for managing hyponatremia in hospitalized patients.	2007 Feb 1	17244874
Clinical trials update from the American Heart Association 2006: OAT, SALT 1 and 2, MAGIC, ABCD, PABA-CHF, IMPROVE-CHF, and percutaneous mitral annuloplasty.	2007 Jan	17188569
Role of vasopressin in rat distal colon function.	2007 Jan 15	17082233
[Arginine vasopressin antagonism--new treatment option in chronic heart failure].	2007 Jan 18	17237865
Gateways to clinical trials.	2007 Jan-Feb	17344945
Gateways to clinical trials.	2007 Jul-Aug	17922073
[Recent progress in vasopressin research on cardiovascular diseases].	2007 Jun	17657988
Vaptans: a promising therapy in the management of advanced cirrhosis.	2007 Jun	17445935
Arginine vasopressin receptor antagonists for heart failure: a winter climbing to the Everest's tip?	2007 Jun 5	17543635
Multicenter, randomized, double-blind, placebo-controlled study on the effect of oral tolvaptan on left ventricular dilation and function in patients with heart failure and systolic dysfunction.	2007 Jun 5	17543634
Clinical trials update from the American College of Cardiology 2007: ALPHA, EVEREST, FUSION II, VALIDD, PARR-2, REMODEL, SPICE, COURAGE, COACH, REMADHE, pro-BNP for the evaluation of dyspnoea and THIS-diet.	2007 Jun-Jul	17481946
Gateways to clinical trials.	2007 Mar	17440629
Tolvaptan for hyponatremia.	2007 Mar 1	17338053
Tolvaptan for hyponatremia.	2007 Mar 1	17338052
Tolvaptan for hyponatremia.	2007 Mar 1	17338051
Tolvaptan for hyponatremia.	2007 Mar 1	17329708
Climbing the mountain of acute decompensated heart failure: the EVEREST Trials.	2007 Mar 28	17384439
Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials.	2007 Mar 28	17384438
Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial.	2007 Mar 28	17384437
What new drugs can nephrologists look forward to in the next year or two?	2007 May	17457357
Hyponatremia: current treatment strategies and the role of vasopressin antagonists.	2007 May	17405824
[Vasopressin V2-receptor antagonist, tolvaptan, for treatment of heart failure].	2007 May 28	17571379
Current issues for nurse practitioners: Hyponatremia.	2007 Nov	17970857
Hyponatremia and vasopressin antagonism in congestive heart failure.	2007 Nov	17847041
Effects of nonpeptide vasopressin V2 antagonist tolvaptan in rats with heart failure.	2007 Nov 15	17720144
Water in health and disease: new aspects of disturbances in water metabolism.	2007 Oct	17954951
V2 receptor antagonism with tolvaptan in heart failure.	2007 Oct	17922627
Tolvaptan, an orally active vasopressin V(2)-receptor antagonist - pharmacology and clinical trials.	2007 Spring	17445084
Polycystic kidney diseases: from molecular discoveries to targeted therapeutic strategies.	2008 Feb	17975706

Patents

Sample Use Guides

In Vivo Use Guide

The usual starting dose for Samsca (Tolvaptan) is 15 mg administered once daily without regard to meals. Increase the dose to 30 mg once daily, after at least 24 hours, to a maximum of 60 mg once daily, as needed to achieve the desired level of serum sodium. Do not administer Samsca for more than 30 days to minimize the risk of liver injury

Route of Administration: Oral

In Vitro Use Guide

Tolvaptan caused a concentration-dependent inhibition of AVP-induced cAMP production with an apparent IC(50) of ∼10(-10) M.

Name

Type

Language

TOLVAPTAN

Official Name

English

TOLVAPTAN [ORANGE BOOK]

Common Name

English

OPC-41061

Code

English

TOLVAPTAN [MART.]

Common Name

English

JINARC

Brand Name

English

SAMSCA

Brand Name

English

JYNARQUE

Brand Name

English

tolvaptan [INN]

Common Name

English

(±)-4'-((7-CHLORO-2,3,4,5-TETRAHYDRO-5-HYDROXY-1H-1-BENZAZEPIN-1-YL) CARBONYL)-O-TOLU-M-TOLUIDIDE

Common Name

English

OPC-41061(TOLVAPTAN)

Code

English

TOLVAPTAN [EMA EPAR]

Common Name

English

BENZAMIDE, N-(4-((7-CHLORO-2,3,4,5-TETRAHYDRO-5-HYDROXY-1H-1-BENZAZEPIN-1-YL)CARBONYL)-3-METHYLPHENYL)-2-METHYL-

Systematic Name

English

TOLVAPTAN [MI]

Common Name

English

TOLVAPTAN [VANDF]

Common Name

English

TOLVAPTAN [JAN]

Common Name

English

Tolvaptan [WHO-DD]

Common Name

English

TOLVAPTAN [USAN]

Common Name

English

Classification Tree Code System Code

LIVERTOX

NBK548503