isradipine 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
calcium channel blockers, nifedipine derivatives 1511 75695-93-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • isradipine
  • dynacrine
  • isradipin
  • isrodipine
A potent antagonist of CALCIUM CHANNELS that is highly selective for VASCULAR SMOOTH MUSCLE. It is effective in the treatment of chronic stable angina pectoris, hypertension, and congestive cardiac failure.
  • Molecular weight: 371.39
  • Formula: C19H21N3O5
  • CLOGP: 3.92
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 1
  • TPSA: 103.55
  • ALOGS: -3.21
  • ROTB: 6
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
5 mg O
5 mg P

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.01 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 0 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.77 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 19.50 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 1.50 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 26 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.04 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 3.30 hours Lombardo F, Berellini G, Obach RS

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 4.021 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 1.406 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 51.168 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 98.175 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 1.360 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 2.400 % High 1
herg hERG pIC50 4.930 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 71.945 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 266.686 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 1.350 % High 1
kinase-safety-class ACVR2B,AXL,BRAF,BTK,CAMK2D,CDK5,CDK9,DYRK1B,EIF2AK3,EPHB4,ERBB2,GRK2,ITK,MAPK10,MAPK7,MAPKAPK2,NTRK2,PDK1,PDK4,PDPK1,PIK3CB,PIK3CG,PRKDC,STK33,TEK 25
kinase-selectivity-class AXL,BRAF,GRK2,PDK4,PIK3CD 5
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 1.663 High 1
mh-clint Mouse hepatocyte intrinsic clearance 103.039 High 1
mppb Mouse plasma protein binding (% unbound) 0.900 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 4.875 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 1.590 % High 1
rh-clint Rat hepatocyte intrinsic clearance 229.087 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 14.180 % High 1
rppb Rat plasma protein binding (% unbound) 1.360 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 24.322 uM High 1

Approvals:

DateAgencyCompanyOrphan
Dec. 20, 1990 FDA SMITHKLINE BEECHAM

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Drug interaction 47.44 37.77 25 466 276428 90351528

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Retinal disorder 53.32 40.04 9 317 1166 42619843
Diverticulitis intestinal perforated 49.33 40.04 7 319 289 42620720

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Diverticulitis intestinal perforated 45.19 35.09 7 800 550 110587942
Tubulointerstitial nephritis 36.42 35.09 14 793 54270 110534222

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC C08CA03 CARDIOVASCULAR SYSTEM
CALCIUM CHANNEL BLOCKERS
SELECTIVE CALCIUM CHANNEL BLOCKERS WITH MAINLY VASCULAR EFFECTS
Dihydropyridine derivatives
FDA CS M0006414 Dihydropyridines
FDA MoA N0000000069 Calcium Channel Antagonists
FDA EPC N0000175421 Dihydropyridine Calcium Channel Blocker
CHEBI has role CHEBI:35476 antipsychotic agent
CHEBI has role CHEBI:35554 cardiovascular drug
CHEBI has role CHEBI:35674 antihypertensive agent
CHEBI has role CHEBI:48407 antiparkinson drug
MeSH PA D000077264 Calcium-Regulating Hormones and Agents
MeSH PA D000959 Antihypertensive Agents
MeSH PA D002121 Calcium Channel Blockers
MeSH PA D002317 Cardiovascular Agents
MeSH PA D014665 Vasodilator Agents
MeSH PA D049990 Membrane Transport Modulators

Related Drugs by ATC class:

C08CA Dihydropyridine derivatives 17 drugs
amlodipinebarnidipinebenidipinecelecoxibcilnidipineclevidipinefelodipinelacidipinelercanidipinelevamlodipinemanidipinenicardipine show all 17 →

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Hypertensive disorder indication 38341003 DOID:10763
Angina pectoris off-label use 194828000
Raynaud's phenomenon off-label use 266261006
Myocardial infarction contraindication 22298006 DOID:5844
Low blood pressure contraindication 45007003
Chronic heart failure contraindication 48447003
Coronary arteriosclerosis contraindication 53741008 DOID:3393
Disease of liver contraindication 235856003 DOID:409
Peripheral edema contraindication 271809000




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 2.23 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Voltage-dependent L-type calcium channel subunit alpha-1D Ion channel GATING INHIBITOR IC50 9.30 IUPHAR CHEMBL
Voltage-dependent L-type calcium channel subunit alpha-1C Ion channel GATING INHIBITOR IC50 8.80 IUPHAR CHEMBL
Voltage-dependent T-type calcium channel subunit alpha-1H Ion channel Ki 5.51 WOMBAT-PK
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 4.30 CHEMBL
Nuclear receptor subfamily 1 group I member 2 Nuclear hormone receptor WOMBAT-PK
Voltage-dependent L-type calcium channel subunit alpha-1C Ion channel IC50 6.97 CHEMBL
Voltage-dependent L-type calcium channel subunit alpha-1D Ion channel IC50 6.66 CHEMBL
Voltage-dependent L-type calcium channel subunit alpha-1F Ion channel GATING INHIBITOR IC50 6.70 IUPHAR
Voltage-dependent L-type calcium channel subunit alpha-1C Ion channel GATING INHIBITOR IC50 7.50 IUPHAR

External reference:

IDSource
4019560 VUID
N0000147660 NUI
D00349 KEGG_DRUG
4019560 VANDF
C0071304 UMLSCUI
CHEBI:6073 CHEBI
CHEMBL399539 ChEMBL_ID
CHEMBL1648 ChEMBL_ID
CHEMBL400875 ChEMBL_ID
DB00270 DRUGBANK_ID
D017275 MESH_DESCRIPTOR_UI
3784 PUBCHEM_CID
4488 IUPHAR_LIGAND_ID
5724 INN_ID
YO1UK1S598 UNII
33910 RXNORM
4939 MMSL
73302 MMSL
d00270 MMSL
003570 NDDF
108533002 SNOMEDCT_US
386862002 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Isradipine HUMAN PRESCRIPTION DRUG LABEL 1 16252-539 CAPSULE 2.50 mg ORAL ANDA 20 sections
Isradipine HUMAN PRESCRIPTION DRUG LABEL 1 16252-540 CAPSULE 5 mg ORAL ANDA 20 sections
Isradipine HUMAN PRESCRIPTION DRUG LABEL 1 42291-062 CAPSULE 2.50 mg ORAL ANDA 20 sections
Isradipine HUMAN PRESCRIPTION DRUG LABEL 1 64850-910 CAPSULE 2.50 mg ORAL ANDA 17 sections
Isradipine HUMAN PRESCRIPTION DRUG LABEL 1 64850-911 CAPSULE 5 mg ORAL ANDA 17 sections
Isradipine HUMAN PRESCRIPTION DRUG LABEL 1 68151-1333 CAPSULE 5 mg ORAL ANDA 20 sections