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disopyramide 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |
| Stem definition | Drug id | CAS RN |
|---|---|---|
| class I antiarrhythmics, disopyramide derivatives | 926 | 3737-09-5 |
Description:
| Molecule | Description |
|---|---|
|
Synonyms:
|
A class I anti-arrhythmic agent (one that interferes directly with the depolarization of the cardiac membrane and thus serves as a membrane-stabilizing agent) with a depressant action on the heart similar to that of guanidine. It also possesses some anticholinergic and local anesthetic properties.
Legend: OFP - off patent OFM - off market ONP - on patent |
Drug dosage:
| Dose | Unit | Route |
|---|---|---|
| 0.40 | g | O |
| 0.40 | g | P |
ADMET properties:
| Property | Value | Reference |
|---|---|---|
| BDDCS (Biopharmaceutical Drug Disposition Classification System) | 3 | Benet LZ, Broccatelli F, Oprea TI |
| S (Water solubility) | 1 mg/mL | Benet LZ, Broccatelli F, Oprea TI |
| EoM (Fraction excreted unchanged in urine) | 55 % | Benet LZ, Broccatelli F, Oprea TI |
| MRTD (Maximum Recommended Therapeutic Daily Dose) | 5.89 µM/kg/day | Contrera JF, Matthews EJ, Kruhlak NL, Benz RD |
| BA (Bioavailability) | 83 % | Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H |
| Vd (Volume of distribution) | 0.52 L/kg | Lombardo F, Berellini G, Obach RS |
| CL (Clearance) | 0.90 mL/min/kg | Lombardo F, Berellini G, Obach RS |
| fu (Fraction unbound in plasma) | 0.16 % | Lombardo F, Berellini G, Obach RS |
| t_half (Half-life) | 7 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 | -0.078 | High | 1 | |
| caco2-efflux | Caco-2 efflux ratio (BA/AB) | 5.105 | High | 1 | |
| caco2-intrinsic-papp | Caco-2 intrinsic apparent permeability | 4.477 | 10^-6 cm/s | High | 1 |
| dh-clint | Dog hepatocyte intrinsic clearance | 2.917 | uL/min/10^6 cells | High | 1 |
| dppb | Dog plasma protein binding (% unbound) | 64.800 | % | High | 1 |
| fcs-ppb | Fetal calf serum protein binding (% unbound) | 59.270 | % | High | 1 |
| herg | hERG pIC50 | 5.020 | pIC50 | High | 1 |
| hh-clint | Human hepatocyte intrinsic clearance | 1.069 | uL/min/10^6 cells | High | 1 |
| hlm-clint | Human liver microsomal intrinsic clearance | 3.972 | uL/min/mg protein | High | 1 |
| hppb | Human plasma protein binding (% unbound) | 59.500 | % | High | 1 |
| kinase-safety-class | ACVR2A,ACVR2B,AKT2,AXL,BRAF,CAMK2B,CAMK2D,CDK5,CDK9,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,ITK,MAP3K7,MAPK12,MAPK7,NTRK2,PDK2,PDK4,PRKDC,SIK2,SIK3,TEK,TGFBR1 | 26 | |||
| kinase-selectivity-class | AXL,EIF2AK3,PDK4 | 3 | |||
| mdck-mdr1-efflux | MDCK-MDR1 efflux ratio | 3.758 | High | 1 | |
| mh-clint | Mouse hepatocyte intrinsic clearance | 24.155 | High | 1 | |
| mppb | Mouse plasma protein binding (% unbound) | 72.960 | High | 1 | |
| nih-mdck-mdr1-efflux | NIH MDCK-MDR1 efflux ratio | 10.186 | High | 1 | |
| pfas-class | PFAS structural alert (1 = True, 0 = False) | 0 | |||
| pppb | Pig plasma protein binding (% unbound) | 75.250 | % | High | 1 |
| rh-clint | Rat hepatocyte intrinsic clearance | 15.241 | uL/min/10^6 cells | High | 1 |
| rh-fuinc | Rat hepatocyte fraction unbound in incubation | 83.330 | % | High | 1 |
| rppb | Rat plasma protein binding (% unbound) | 67.380 | % | High | 1 |
| solubility-dd | Solubility at pH 7.4 in DMSO | 864.968 | uM | High | 1 |
Approvals:
| Date | Agency | Company | Orphan |
|---|---|---|---|
| Sept. 1, 1977 | FDA | GD SEARLE LLC |
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 |
|---|---|---|---|---|---|---|
| Electrocardiogram QT prolonged | 40.55 | 30.17 | 17 | 737 | 72439 | 90555254 |
| Left atrial volume increased | 40.53 | 30.17 | 5 | 749 | 62 | 90627631 |
| Mitral valve stenosis | 31.68 | 30.17 | 6 | 748 | 1353 | 90626340 |
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 |
|---|---|---|---|---|---|---|
| Torsade de pointes | 39.93 | 33.49 | 11 | 532 | 8583 | 42612209 |
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 |
|---|---|---|---|---|---|---|
| Electrocardiogram QT prolonged | 55.24 | 28.05 | 26 | 1201 | 108934 | 110479138 |
| Bradycardia | 46.50 | 28.05 | 26 | 1201 | 155491 | 110432581 |
| Hypoglycaemia | 41.90 | 28.05 | 22 | 1205 | 116082 | 110471990 |
| Left atrial volume increased | 36.93 | 28.05 | 5 | 1222 | 98 | 110587974 |
| Torsade de pointes | 34.73 | 28.05 | 12 | 1215 | 22588 | 110565484 |
| Atrial fibrillation | 30.33 | 28.05 | 23 | 1204 | 229619 | 110358453 |
| Mitral valve stenosis | 29.76 | 28.05 | 6 | 1221 | 1396 | 110586676 |
FDA Adverse Event Reporting System (Pediatric)
None
Pharmacologic Action:
| Source | Code | Description |
|---|---|---|
| ATC | C01BA03 | CARDIOVASCULAR SYSTEM CARDIAC THERAPY ANTIARRHYTHMICS, CLASS I AND III Antiarrhythmics, class Ia |
| FDA EPC | N0000175426 | Antiarrhythmic |
| MeSH PA | D000889 | Anti-Arrhythmia Agents |
| MeSH PA | D002317 | Cardiovascular Agents |
| MeSH PA | D026941 | Sodium Channel Blockers |
| MeSH PA | D049990 | Membrane Transport Modulators |
| MeSH PA | D061567 | Voltage-Gated Sodium Channel Blockers |
| CHEBI has role | CHEBI:35554 | cardiovascular drug |
| CHEBI has role | CHEBI:38070 | anti-arrhythmia drug |
Related Drugs by ATC class:
C01BA Antiarrhythmics, class Ia 7 drugs
Drug Use | Suggest Off label Use Form| |View source of the data|
| Disease | Relation | SNOMED_ID | DOID |
|---|---|---|---|
| Ventricular arrhythmia | indication | 44103008 | |
| Paroxysmal supraventricular tachycardia | off-label use | 67198005 | |
| Atrial flutter | contraindication | 5370000 | |
| Hyperkalemia | contraindication | 14140009 | |
| Complete atrioventricular block | contraindication | 27885002 | |
| Hypokalemia | contraindication | 43339004 | |
| Low blood pressure | contraindication | 45007003 | |
| Chronic heart failure | contraindication | 48447003 | |
| Atrial fibrillation | contraindication | 49436004 | DOID:0060224 |
| Myocarditis | contraindication | 50920009 | DOID:820 |
| Acute nephropathy | contraindication | 58574008 | |
| Cardiomyopathy | contraindication | 85898001 | DOID:0050700 |
| Cardiogenic shock | contraindication | 89138009 | |
| Kidney disease | contraindication | 90708001 | DOID:557 |
| Myasthenia gravis | contraindication | 91637004 | DOID:437 |
| Prolonged QT interval | contraindication | 111975006 | |
| Second degree atrioventricular block | contraindication | 195042002 | |
| Decompensated cardiac failure | contraindication | 195111005 | |
| Disease of liver | contraindication | 235856003 | DOID:409 |
| Hypoglycemic disorder | contraindication | 237630007 | |
| Benign prostatic hyperplasia | contraindication | 266569009 | |
| Retention of urine | contraindication | 267064002 | |
| Angle-closure glaucoma | contraindication | 392291006 | DOID:13550 |
| Congenital long QT syndrome | contraindication | 442917000 | |
| Increased Intraocular Pressure after Ocular Procedure | contraindication |
🐶 Veterinary Drug Use
None
🐶 Veterinary products
None
Acid dissociation constants calculated using MoKa v3.0.0
| Dissociation level | Dissociation constant | Type (acidic/basic) |
|---|---|---|
| pKa1 | 13.71 | acidic |
| pKa2 | 9.79 | Basic |
| pKa3 | 4.23 | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Sodium channel protein type 5 subunit alpha | Ion channel | BLOCKER | WOMBAT-PK | CHEMBL | |||||
| Potassium voltage-gated channel subfamily H member 2 | Ion channel | IC50 | 4.04 | WOMBAT-PK | |||||
| Histamine H1 receptor | GPCR | Ki | 5.57 | WOMBAT-PK | |||||
| Muscarinic acetylcholine receptor M1 | GPCR | WOMBAT-PK | |||||||
| Muscarinic acetylcholine receptor M2 | GPCR | WOMBAT-PK | |||||||
| Muscarinic acetylcholine receptor M3 | GPCR | WOMBAT-PK | |||||||
| G protein-activated inward rectifier potassium channel 4 | Ion channel | IC50 | 4.92 | WOMBAT-PK | |||||
| Solute carrier family 22 member 1 | Transporter | IC50 | 4.09 | CHEMBL | |||||
| Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 | Ion channel | IC50 | 3.60 | WOMBAT-PK |
External reference:
| ID | Source |
|---|---|
| 4019729 | VUID |
| N0000147821 | NUI |
| D00303 | KEGG_DRUG |
| 22059-60-5 | SECONDARY_CAS_RN |
| 203178 | RXNORM |
| 4017844 | VANDF |
| 4019729 | VANDF |
| C0012702 | UMLSCUI |
| CHEBI:4657 | CHEBI |
| DP0 | PDB_CHEM_ID |
| CHEMBL517 | ChEMBL_ID |
| DB00280 | DRUGBANK_ID |
| CHEMBL1201020 | ChEMBL_ID |
| D004206 | MESH_DESCRIPTOR_UI |
| 3114 | PUBCHEM_CID |
| 7167 | IUPHAR_LIGAND_ID |
| 1307 | INN_ID |
| GFO928U8MQ | UNII |
| 2690 | MMSL |
| 4622 | MMSL |
| d00214 | MMSL |
| 000623 | NDDF |
| 000624 | NDDF |
| 372844004 | SNOMEDCT_US |
| 49565007 | SNOMEDCT_US |
| 76759004 | SNOMEDCT_US |
| 54687-36-4 | SECONDARY_CAS_RN |
| GFO928U8MQ | INXIGHT DRUGS |
Pharmaceutical products:
| Product | Category | Ingredients | NDC | Form | Quantity | Route | Marketing | Label |
|---|---|---|---|---|---|---|---|---|
| Norpace CR | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0025-2732 | CAPSULE, EXTENDED RELEASE | 100 mg | ORAL | NDA | 25 sections |
| Norpace CR | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0025-2742 | CAPSULE, EXTENDED RELEASE | 150 mg | ORAL | NDA | 25 sections |
| Norpace | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0025-2752 | CAPSULE, GELATIN COATED | 100 mg | ORAL | NDA | 25 sections |
| Norpace | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0025-2762 | CAPSULE, GELATIN COATED | 150 mg | ORAL | NDA | 25 sections |
| Disopyramide Phosphate | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0093-3127 | CAPSULE | 100 mg | ORAL | ANDA | 19 sections |
| Disopyramide Phosphate | HUMAN PRESCRIPTION DRUG LABEL | 1 | 0093-3129 | CAPSULE | 150 mg | ORAL | ANDA | 19 sections |
| Disopyramide Phosphate | HUMAN PRESCRIPTION DRUG LABEL | 1 | 59762-0386 | CAPSULE, GELATIN COATED | 100 mg | ORAL | NDA AUTHORIZED GENERIC | 28 sections |
| Disopyramide Phosphate | HUMAN PRESCRIPTION DRUG LABEL | 1 | 59762-0400 | CAPSULE, GELATIN COATED | 150 mg | ORAL | NDA AUTHORIZED GENERIC | 28 sections |
| Norpace | HUMAN PRESCRIPTION DRUG LABEL | 1 | 68151-0526 | CAPSULE, GELATIN COATED | 100 mg | ORAL | NDA | 26 sections |
| Norpace | HUMAN PRESCRIPTION DRUG LABEL | 1 | 68151-0527 | CAPSULE, GELATIN COATED | 150 mg | ORAL | NDA | 26 sections |
| Disopyramide Phosphate | HUMAN PRESCRIPTION DRUG LABEL | 1 | 68151-0528 | CAPSULE | 150 mg | ORAL | ANDA | 19 sections |
| Disopyramide Phosphate | HUMAN PRESCRIPTION DRUG LABEL | 1 | 68151-3858 | CAPSULE | 100 mg | ORAL | ANDA | 19 sections |
| DISOPYRAMIDE PHOSPHATE | HUMAN PRESCRIPTION DRUG LABEL | 1 | 75907-026 | CAPSULE | 150 mg | ORAL | ANDA | 26 sections |
| DISOPYRAMIDE PHOSPHATE | HUMAN PRESCRIPTION DRUG LABEL | 1 | 75907-027 | CAPSULE | 100 mg | ORAL | ANDA | 26 sections |