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Drug

D1129 | tolvaptan

Molecular Formula C26H25ClN2O3
Molecular Weight 448.9
Structure
State solid
Clearance 4 mL/min/kg (post-oral dosing).
Volume of distribution Healthy subjects: 3L/kg; slightly higher in heart failure patients.
Route of elimination Fecal- very little renal elimination (<1% is excreted unchanged in the urine)
Protein binding 99% bound
Half life Terminal half life, oral dose = 12 hours.
Absorption Tmax, Healthy subjects: 2 - 4 hours; Cmax, Healthy subjects, 30 mg: 374 ng/mL; Cmax, Healthy subjects, 90 mg: 418 ng/mL; Cmax, heart failure patients, 30 mg: 460 ng/mL; Cmax, heart failure patients, 90 mg: 723 ng/mL; AUC(0-24 hours), 60 mg: 3.71 μg·h/mL; AUC(∞), 60 mg: 4.55 μg·h/mL; The pharmacokinetic properties of tolvaptan are stereospecific, with a steady-state ratio of the S-(-) to the R-(+) enantiomer of about 3. The absolute bioavailability of tolvaptan is unknown. At least 40% of the dose is absorbed as tolvaptan or metabolites. Food does not impact the bioavailability of tolvaptan.

C

C03XA01 Tolvaptan


[C03XA] Vasopressin antagonists


[C03X] OTHER DIURETICS


[C03] DIURETICS


[C] Cardiovascular system

Toxicity Dose Time Species Model Method Action Positive criterion Reference
MEMBRANE POTENTIAL 17.44±8.01 human qHTS-HepG2 MMP assay decrease IC50 163
MEMBRANE POTENTIAL 19.45 human HepG2 MMP assay decrease IC50 163
MEMBRANE POTENTIAL 17.41±2.00 rat hepatocytes MMP assay decrease IC50 163

Pictogram Signal Statements Precautionary Statement Codes
Warning

Aggregated GHS information provided by 2 companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.


H361 (100%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]


H362 (100%): May cause harm to breast-fed children [Reproductive toxicity, effects on or via lactation]


Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.


 P201, P202, P260, P263, P264, P270, P281, P308+P313, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)

H413: May cause long lasting harmful effects to aquatic life [Hazardous to the aquatic environment, long-term hazard]


 P273, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)

Organism Test type Route Dose (normalized dose) Effect Source
guinea pig LD50 intraperitoneal 198mg/kg (198mg/kg) Journal of Pharmacology and Experimental Therapeutics. Vol. 77, Pg. 54, 1943.
mouse LD50 intraperitoneal 991mg/kg (991mg/kg) lungs, thorax, or respiration: pleural effusion Journal of Pharmacology and Experimental Therapeutics. Vol. 77, Pg. 54, 1943.


  • (+-)-4'-((7-Chloro-2,3,4,5-tetrahydro-5-hydroxy-1H-1-benzazepin-1-yl) carbonyl)-o-tolu-m-toluidide (+-)-4'-((7-Chloro-2,3,4,5-tetrahydro-5-hydroxy-1H-1-benzazepin-1-yl)carbonyl)-o-tolu-m-toluidide 150683-30-0
    4CA-1265 5-hydroxy-7-chloro-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1h-benzazepine 683T300
    7-Chloro-5-hydroxy-1-(2-methyl-4-(2-methylbenzoylamino)benzoyl)2,3,4,5-tetrahydro-1H-1-benzazepine 7-chloro-5-hydroxy-1-[2-methyl-4-(2-methyl benzoyl amino) benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepine 7-chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoylamino) benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepine
    7-chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepine AB0009995 AB01565822_02
    AB2000685 AC-22748 AK-33401
    AKOS015994735 AM20090726 ANW-59865
    API0024498 AX8158397 BDBM35723
    Benzamide, N-(4-((7-chloro-2,3,4,5-tetrahydro-5-hydroxy-1H-1-benzazepin-1-yl)carbonyl)-3-methylphenyl)-2-methyl- Benzamide, N-[4-[(7-chloro-2,3,4,5-tetrahydro-5-hydroxy-1H-1-benzazepin-1-yl)carbonyl]-3-methylphenyl]-2-methyl- C26H25ClN2O3
    CAS-150683-30-0 CHEBI:32246 CHEMBL344159
    CS-0572 CT0200 CTK8B8272
    DSSTox_CID_28706 DSSTox_GSID_48780 DSSTox_RID_82975
    DTXSID3048780 FT-0645839 GTPL2226
    GYHCTFXIZSNGJT-UHFFFAOYSA-N HMS3604L08 HMS3656K20
    HMS3744A09 HSDB 8196 HY-17000
    KS-1315 L001628 N-(4-(7-Chloro-5-hydroxy-2,3,4,5-tetrahydro-1H-benzo[b]-azepine-1-carbonyl)-3-methylphenyl)-2-methylbenzamide
    N-(4-(7-Chloro-5-hydroxy-2,3,4,5-tetrahydro-1H-benzo[b]azepine-1-carbonyl)-3-methylphenyl)-2-methylbenzamide N-[4-(7-Chloro-5-hydroxy-2,3,4,5-tetrahydro-benzo[b]azepine-1-carbonyl)-3-methyl-phenyl]-2-methyl-benzamide N-[4-(7-chloro-5-hydroxy-2,3,4,5-tetrahydro-1-benzazepine-1-carbonyl)-3-methylphenyl]-2-methylbenzamide
    N-[4-(7-chloro-5-hydroxy2,3,4,5-tetrahydro-1-benzazepine-1-carbonyl)-3-methylphenyl]-2-methylbenzamide N-[4-(9-chloro-6-hydroxy-2-azabicyclo[5.4.0]undeca-8,10,12-triene-2-carbonyl)-3-methyl-phenyl]-2-methyl-benzamide; N-[4-[(7-Chloro-2,3,4,5-tetrahydro-5-hydroxy-1H-1-benzazepin-1-yl)carbonyl]-3-methylphenyl]-2-methylbenzamide
    NCGC00183001-01 OPC 41061 OPC-41061
    OPC-41061(TOLVAPTAN) PDSP1_001738 PDSP2_001721
    Q426132 SCHEMBL242421 SR-01000942265
    SR-01000942265-1 ST24031322 SW219182-1
    Samsca Samsca;OPC-41061 TC-148610
    Tolvaptan Tolvaptan (OPC-41061) Tolvaptan [USAN:INN:BAN]
    Tolvaptan, >=98% (HPLC), powder Tox21_113256 ZINC000000538658
    benzazepine derivative, 32 s2593 tolvaptan-opc-41061

    DrugBank DB06212
    CAS Number 150683-30-0, 331947-66-1, 36376-47-3
    PubChem Compound 216237
    KEGG Drug D01213
    ChEBI 32246