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hydroflumethiazide 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |
| Stem definition | Drug id | CAS RN |
|---|---|---|
| diuretics, chlorothiazide derivatives | 1392 | 135-09-1 |
Description:
| Molecule | Description |
|---|---|
|
Synonyms:
|
A thiazide diuretic with actions and uses similar to those of HYDROCHLOROTHIAZIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p822)
Legend: OFP - off patent OFM - off market ONP - on patent |
Drug dosage:
| Dose | Unit | Route |
|---|---|---|
| 25 | mg | O |
| 25 | mg | O |
ADMET properties:
| Property | Value | Reference |
|---|---|---|
| BDDCS (Biopharmaceutical Drug Disposition Classification System) | 3 | Benet LZ, Broccatelli F, Oprea TI |
| S (Water solubility) | 0.30 mg/mL | Benet LZ, Broccatelli F, Oprea TI |
| EoM (Fraction excreted unchanged in urine) | 90 % | Benet LZ, Broccatelli F, Oprea TI |
| MRTD (Maximum Recommended Therapeutic Daily Dose) | 10.05 µM/kg/day | Contrera JF, Matthews EJ, Kruhlak NL, Benz RD |
| BA (Bioavailability) | 50 % | Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H |
| Vd (Volume of distribution) | 2.20 L/kg | Lombardo F, Berellini G, Obach RS |
| CL (Clearance) | 9.70 mL/min/kg | Lombardo F, Berellini G, Obach RS |
| t_half (Half-life) | 5.20 hours | Lombardo F, Berellini G, Obach RS |
Predicted pharmacokinetic/toxicological properties (PK-AZ):
| Property | Description | Value | Unit | Confidence | Similarity |
|---|---|---|---|---|---|
| azlogd74 | LogD at pH 7.4 | 0.393 | High | 1 | |
| caco2-efflux | Caco-2 efflux ratio (BA/AB) | 8.299 | High | 1 | |
| caco2-intrinsic-papp | Caco-2 intrinsic apparent permeability | 0.594 | 10^-6 cm/s | High | 1 |
| dh-clint | Dog hepatocyte intrinsic clearance | 2.858 | uL/min/10^6 cells | High | 1 |
| dppb | Dog plasma protein binding (% unbound) | 35.200 | % | High | 1 |
| fcs-ppb | Fetal calf serum protein binding (% unbound) | 45.520 | % | High | 1 |
| herg | hERG pIC50 | 4.150 | pIC50 | High | 1 |
| hh-clint | Human hepatocyte intrinsic clearance | 1.127 | uL/min/10^6 cells | High | 1 |
| hlm-clint | Human liver microsomal intrinsic clearance | 3.069 | uL/min/mg protein | High | 1 |
| hppb | Human plasma protein binding (% unbound) | 36.580 | % | High | 1 |
| kinase-safety-class | ACVR2A,ACVR2B,AURKA,AXL,BRAF,BTK,CAMK2D,CDK5,CDK9,DYRK1B,EGFR,EIF2AK3,ERBB2,GRK2,ITK,MAP2K6,MAPK10,MAPK7,MAPKAPK2,NTRK2,PDK1,PDK2,PDK4,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PRKDC,SIK2,STK33,SYK,TEK,ZAP70 | 33 | |||
| kinase-selectivity-class | MAP2K6,PDK1 | 2 | |||
| mdck-mdr1-bcrp-efflux | MDCK-MDR1-BCRP efflux ratio | 0.627 | High | 1 | |
| mdck-mdr1-efflux | MDCK-MDR1 efflux ratio | 0.904 | High | 1 | |
| mh-clint | Mouse hepatocyte intrinsic clearance | 1.849 | High | 1 | |
| mppb | Mouse plasma protein binding (% unbound) | 32.520 | High | 1 | |
| nih-mdck-mdr1-efflux | NIH MDCK-MDR1 efflux ratio | 1.816 | High | 1 | |
| pfas-class | PFAS structural alert (1 = True, 0 = False) | 1 | |||
| pppb | Pig plasma protein binding (% unbound) | 52.300 | % | High | 1 |
| rat-kpuu-brain | Rat brain Kpuu | 0.011 | % | High | 1 |
| rh-clint | Rat hepatocyte intrinsic clearance | 1.349 | uL/min/10^6 cells | High | 1 |
| rh-fuinc | Rat hepatocyte fraction unbound in incubation | 87.400 | % | High | 1 |
| rppb | Rat plasma protein binding (% unbound) | 35.780 | % | High | 1 |
| solubility-dd | Solubility at pH 7.4 in DMSO | 668.344 | uM | High | 1 |
Approvals:
| Date | Agency | Company | Orphan |
|---|---|---|---|
| July 22, 1959 | FDA | SHIRE LLC |
FDA Adverse Event Reporting System (Female)
None
FDA Adverse Event Reporting System (Male)
None
FDA Adverse Event Reporting System (Geriatric)
None
FDA Adverse Event Reporting System (Pediatric)
None
Pharmacologic Action:
| Source | Code | Description |
|---|---|---|
| ATC | C03AA02 | CARDIOVASCULAR SYSTEM DIURETICS LOW-CEILING DIURETICS, THIAZIDES Thiazides, plain |
| ATC | C03AB02 | CARDIOVASCULAR SYSTEM DIURETICS LOW-CEILING DIURETICS, THIAZIDES Thiazides and potassium in combination |
| ATC | C03AH02 | CARDIOVASCULAR SYSTEM DIURETICS LOW-CEILING DIURETICS, THIAZIDES Thiazides, combinations with psycholeptics and/or analgesics |
| FDA CS | M0471776 | Thiazides |
| FDA PE | N0000175359 | Increased Diuresis |
| FDA EPC | N0000175419 | Thiazide Diuretic |
| MeSH PA | D000959 | Antihypertensive Agents |
| MeSH PA | D002317 | Cardiovascular Agents |
| MeSH PA | D004232 | Diuretics |
| MeSH PA | D045283 | Natriuretic Agents |
| MeSH PA | D049990 | Membrane Transport Modulators |
| MeSH PA | D049993 | Sodium Chloride Symporter Inhibitors |
| CHEBI has role | CHEBI:35498 | diuretic |
| CHEBI has role | CHEBI:35554 | cardiovascular drug |
| CHEBI has role | CHEBI:35674 | antihypertensive agent |
Related Drugs by ATC class:
C03AA Thiazides, plain 9 drugs
C03AB Thiazides and potassium in combination 8 drugs
C03AH Thiazides, combinations with psycholeptics and/or analgesics 1 drug
Drug Use | Suggest Off label Use Form| |View source of the data|
| Disease | Relation | SNOMED_ID | DOID |
|---|---|---|---|
| Hypertensive disorder | indication | 38341003 | DOID:10763 |
| Edema | indication | 267038008 | |
| Calcium renal calculus | off-label use | 427649000 | |
| Suicidal thoughts | contraindication | 6471006 | |
| Peptic ulcer | contraindication | 13200003 | DOID:750 |
| Chronic disease of respiratory system | contraindication | 17097001 | |
| Electroconvulsive therapy | contraindication | 23835007 | |
| Depressive disorder | contraindication | 35489007 | |
| Conduction disorder of the heart | contraindication | 44808001 | |
| Chronic heart failure | contraindication | 48447003 | |
| Ulcerative colitis | contraindication | 64766004 | DOID:8577 |
| Epilepsy | contraindication | 84757009 | DOID:1826 |
| Kidney disease | contraindication | 90708001 | DOID:557 |
| Calculus in biliary tract | contraindication | 266474003 |
🐶 Veterinary Drug Use
None
🐶 Veterinary products
None
Acid dissociation constants calculated using MoKa v3.0.0
| Dissociation level | Dissociation constant | Type (acidic/basic) |
|---|---|---|
| pKa1 | 8.86 | acidic |
| pKa2 | 10.57 | acidic |
| pKa3 | 1.75 | Basic |
Orange Book patent data (new drug applications)
None
Orange Book exclusivity data (new drug applications)
None
Bioactivity Summary:
| Target | Class | Pharos | UniProt | Action | Type | Activity value (-log[M]) | Mechanism action | Bioact source | MoA source |
|---|---|---|---|---|---|---|---|---|---|
| Solute carrier family 12 member 3 | Transporter | INHIBITOR | A2 | 7.37 | WOMBAT-PK | CHEMBL |
External reference:
| ID | Source |
|---|---|
| 4018143 | VUID |
| N0000146480 | NUI |
| D00654 | KEGG_DRUG |
| 4018143 | VANDF |
| C0020273 | UMLSCUI |
| CHEBI:5784 | CHEBI |
| HFZ | PDB_CHEM_ID |
| CHEMBL1763 | ChEMBL_ID |
| DB00774 | DRUGBANK_ID |
| D006857 | MESH_DESCRIPTOR_UI |
| 3647 | PUBCHEM_CID |
| 7197 | IUPHAR_LIGAND_ID |
| 895 | INN_ID |
| 501CFL162R | UNII |
| 5495 | RXNORM |
| 4845 | MMSL |
| d00645 | MMSL |
| 002296 | NDDF |
| 18914005 | SNOMEDCT_US |
| 395946004 | SNOMEDCT_US |
| 501CFL162R | INXIGHT DRUGS |
Pharmaceutical products:
None