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diazoxide ๐ถ Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |
| Stem definition | Drug id | CAS RN |
|---|---|---|
| diuretics, chlorothiazide derivatives | 854 | 364-98-7 |
Description:
| Molecule | Description |
|---|---|
|
Synonyms:
|
A benzothiadiazine derivative that is a peripheral vasodilator used for hypertensive emergencies. It lacks diuretic effect, apparently because it lacks a sulfonamide group.
Legend: OFP - off patent OFM - off market ONP - on patent |
Drug dosage:
| Dose | Unit | Route |
|---|---|---|
| 0.30 | g | P |
ADMET properties:
| Property | Value | Reference |
|---|---|---|
| BDDCS (Biopharmaceutical Drug Disposition Classification System) | 2 | Benet LZ, Broccatelli F, Oprea TI |
| S (Water solubility) | 0.07 mg/mL | Bocci G, Oprea TI, Benet LZ |
| EoM (Fraction excreted unchanged in urine) | 35 % | Benet LZ, Broccatelli F, Oprea TI |
| MRTD (Maximum Recommended Therapeutic Daily Dose) | 34.68 ยตM/kg/day | Contrera JF, Matthews EJ, Kruhlak NL, Benz RD |
| BA (Bioavailability) | 90 % | Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H |
| Vd (Volume of distribution) | 0.21 L/kg | Lombardo F, Berellini G, Obach RS |
| CL (Clearance) | 0.06 mL/min/kg | Lombardo F, Berellini G, Obach RS |
| fu (Fraction unbound in plasma) | 0.06 % | Lombardo F, Berellini G, Obach RS |
| t_half (Half-life) | 48 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 | 1.004 | High | 1 | |
| caco2-efflux | Caco-2 efflux ratio (BA/AB) | 4.236 | High | 1 | |
| caco2-intrinsic-papp | Caco-2 intrinsic apparent permeability | 12.764 | 10^-6 cm/s | High | 1 |
| dh-clint | Dog hepatocyte intrinsic clearance | 2.884 | uL/min/10^6 cells | High | 1 |
| dppb | Dog plasma protein binding (% unbound) | 21.170 | % | High | 1 |
| fcs-ppb | Fetal calf serum protein binding (% unbound) | 26.230 | % | High | 1 |
| herg | hERG pIC50 | 4.271 | pIC50 | High | 1 |
| hh-clint | Human hepatocyte intrinsic clearance | 0.953 | uL/min/10^6 cells | High | 1 |
| hlm-clint | Human liver microsomal intrinsic clearance | 3.013 | uL/min/mg protein | High | 1 |
| hppb | Human plasma protein binding (% unbound) | 16.470 | % | High | 1 |
| mdck-mdr1-efflux | MDCK-MDR1 efflux ratio | 3.373 | High | 1 | |
| mh-clint | Mouse hepatocyte intrinsic clearance | 3.540 | High | 1 | |
| mppb | Mouse plasma protein binding (% unbound) | 30.390 | High | 1 | |
| nih-mdck-mdr1-efflux | NIH MDCK-MDR1 efflux ratio | 5.495 | High | 1 | |
| pfas-class | PFAS structural alert (1 = True, 0 = False) | 0 | |||
| pppb | Pig plasma protein binding (% unbound) | 30.100 | % | High | 1 |
| rh-clint | Rat hepatocyte intrinsic clearance | 2.080 | uL/min/10^6 cells | High | 1 |
| rh-fuinc | Rat hepatocyte fraction unbound in incubation | 92.020 | % | High | 1 |
| rppb | Rat plasma protein binding (% unbound) | 12.830 | % | High | 1 |
| solubility-dd | Solubility at pH 7.4 in DMSO | 381.066 | uM | High | 1 |
Approvals:
| Date | Agency | Company | Orphan |
|---|---|---|---|
| Jan. 22, 1973 | FDA |
FDA Adverse Event Reporting System (Female)
| MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
|---|---|---|---|---|---|---|
| Hypoglycaemia | 103.82 | 40.79 | 33 | 672 | 69815 | 90557927 |
| Insulinoma | 90.28 | 40.79 | 11 | 694 | 132 | 90627610 |
| Hyperglycaemic hyperosmolar nonketotic syndrome | 72.44 | 40.79 | 12 | 693 | 1357 | 90626385 |
| Drug ineffective for unapproved indication | 65.11 | 40.79 | 23 | 682 | 66621 | 90561121 |
| Drug ineffective | 53.84 | 40.79 | 59 | 646 | 1384239 | 89243503 |
| Hyperglycaemia | 47.49 | 40.79 | 17 | 688 | 50953 | 90576789 |
FDA Adverse Event Reporting System (Male)
| MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
|---|---|---|---|---|---|---|
| Hypoglycaemia | 76.00 | 44.91 | 28 | 484 | 59826 | 42560997 |
| Drug ineffective | 66.04 | 44.91 | 56 | 456 | 630141 | 41990682 |
| Necrotising colitis | 61.17 | 44.91 | 11 | 501 | 1300 | 42619523 |
FDA Adverse Event Reporting System (Geriatric)
| MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
|---|---|---|---|---|---|---|
| Hypoglycaemia | 149.14 | 37.53 | 50 | 879 | 116054 | 110472316 |
| Insulinoma | 112.22 | 37.53 | 14 | 915 | 190 | 110588180 |
| Drug ineffective | 95.78 | 37.53 | 87 | 842 | 1520453 | 109067917 |
| Drug ineffective for unapproved indication | 63.72 | 37.53 | 26 | 903 | 102812 | 110485558 |
| Hyperglycaemic hyperosmolar nonketotic syndrome | 62.06 | 37.53 | 12 | 917 | 2997 | 110585373 |
| Malignant neoplasm progression | 42.03 | 37.53 | 23 | 906 | 174544 | 110413826 |
| Hyperglycaemia | 40.95 | 37.53 | 18 | 911 | 85072 | 110503298 |
FDA Adverse Event Reporting System (Pediatric)
None
Pharmacologic Action:
| Source | Code | Description |
|---|---|---|
| ATC | C02DA01 | CARDIOVASCULAR SYSTEM ANTIHYPERTENSIVES ARTERIOLAR SMOOTH MUSCLE, AGENTS ACTING ON Thiazide derivatives |
| ATC | V03AH01 | VARIOUS ALL OTHER THERAPEUTIC PRODUCTS ALL OTHER THERAPEUTIC PRODUCTS Drugs for treatment of hypoglycemia |
| MeSH PA | D000959 | Antihypertensive Agents |
| MeSH PA | D002317 | Cardiovascular Agents |
| MeSH PA | D014665 | Vasodilator Agents |
| CHEBI has role | CHEBI:35469 | antidepressant |
| CHEBI has role | CHEBI:35498 | diuretic |
| CHEBI has role | CHEBI:35522 | ฮฒ-adrenergic agonist |
| CHEBI has role | CHEBI:35523 | bronchodilator agent |
| CHEBI has role | CHEBI:35524 | sympathomimetic agent |
| CHEBI has role | CHEBI:35526 | hypoglycemic agent |
| CHEBI has role | CHEBI:35620 | vasodilator agent |
| CHEBI has role | CHEBI:35674 | antihypertensive agent |
| CHEBI has role | CHEBI:38147 | cardiotonic drug |
| CHEBI has role | CHEBI:38633 | sodium channel blocker |
| CHEBI has role | CHEBI:64338 | K-ATP channel agonist |
| CHEBI has role | CHEBI:74518 | anti-obesity agent |
| CHEBI has role | CHEBI:76916 | hyperglycemic agent |
Drug Use | Suggest Off label Use Form| |View source of the data|
| Disease | Relation | SNOMED_ID | DOID |
|---|---|---|---|
| Islet cell hyperplasia | indication | 42681006 | DOID:13317 |
| Hyperinsulinism | indication | 83469008 | DOID:2018 |
| Insulinoma | indication | 302822000 | DOID:3892 |
| Hypertensive urgency | indication | 443482000 | |
| Hypertensive Emergencies | indication | ||
| Hypertensive Emergency associated with Pregnancy | off-label use | ||
| Hyperkalemia | contraindication | 14140009 | |
| Orthostatic hypotension | contraindication | 28651003 | |
| Hyperuricemia | contraindication | 35885006 | DOID:1920 |
| Hypokalemia | contraindication | 43339004 | |
| Body fluid retention | contraindication | 43498006 | |
| Decreased cardiac function | contraindication | 43650005 | |
| Uremia | contraindication | 44730006 | DOID:4676 |
| Chronic heart failure | contraindication | 48447003 | |
| Ketoacidosis | contraindication | 56051008 | |
| Cerebrovascular disease | contraindication | 62914000 | DOID:6713 |
| Diabetes mellitus | contraindication | 73211009 | DOID:9351 |
| Hyperglycemia | contraindication | 80394007 | DOID:4195 |
| Gout | contraindication | 90560007 | DOID:13189 |
| Kidney disease | contraindication | 90708001 | DOID:557 |
| Disease of liver | contraindication | 235856003 | DOID:409 |
| Edema | contraindication | 267038008 | |
| Chronic myocardial ischemia | contraindication | 413844008 | DOID:3393 |
| Hypertension due to Aortic Coarctation | contraindication | ||
| Hypertension due to Arteriovenous Shunt | contraindication |
๐ถ Veterinary Drug Use
None
๐ถ Veterinary products
None
Acid dissociation constants calculated using MoKa v3.0.0
| Dissociation level | Dissociation constant | Type (acidic/basic) |
|---|---|---|
| pKa1 | 8.8 | acidic |
| pKa2 | 5.51 | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Sulfonylurea receptor 1, Kir6.2 | Ion channel | OPENER | EC50 | 4.63 | CHEMBL | CHEMBL | |||
| Nicotinamide phosphoribosyltransferase | Enzyme | Kd | 3.64 | CHEMBL | |||||
| ATP-sensitive inward rectifier potassium channel 11 | Ion channel | ACTIVATOR | EC50 | 4.20 | IUPHAR |
External reference:
| ID | Source |
|---|---|
| 4018795 | VUID |
| N0000147098 | NUI |
| D00294 | KEGG_DRUG |
| 202594 | RXNORM |
| 4018795 | VANDF |
| C0012022 | UMLSCUI |
| CHEBI:4495 | CHEBI |
| CHEMBL181 | ChEMBL_ID |
| DB01119 | DRUGBANK_ID |
| D003981 | MESH_DESCRIPTOR_UI |
| 3019 | PUBCHEM_CID |
| 2409 | IUPHAR_LIGAND_ID |
| 1294 | INN_ID |
| O5CB12L4FN | UNII |
| 2004 | MMSL |
| 4574 | MMSL |
| 72399 | MMSL |
| d00129 | MMSL |
| 000636 | NDDF |
| 387328001 | SNOMEDCT_US |
| 58905004 | SNOMEDCT_US |
| 20J | PDB_CHEM_ID |
Pharmaceutical products:
| Product | Category | Ingredients | NDC | Form | Quantity | Route | Marketing | Label |
|---|---|---|---|---|---|---|---|---|
| Diazoxide | Human Prescription Drug Label | 1 | 0254-1010 | SUSPENSION | 50 mg | ORAL | ANDA | 21 sections |
| Proglycem | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0575-6200 | SUSPENSION | 50 mg | ORAL | NDA | 22 sections |
| Diazoxide | HUMAN PRESCRIPTION DRUG LABEL | 1 | 13517-100 | SUSPENSION | 50 mg | ORAL | ANDA | 23 sections |