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

Stem definitionDrug idCAS RN
local anaesthetics 4 27262-47-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • levobupivacaine
  • chirocain
  • levobupivacaine hydrochloride
  • levobupivacaine HCl
S-enantiomer of bupivacaine, local anaesthetic
  • Molecular weight: 288.44
  • Formula: C18H28N2O
  • CLOGP: 3.69
  • LIPINSKI: 0
  • HAC: 3
  • HDO: 1
  • TPSA: 32.34
  • ALOGS: -3.47
  • ROTB: 5
  • Status: OFM
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 100 mg/mL Bocci G, Oprea TI, Benet LZ
EoM (Fraction excreted unchanged in urine) 0.50 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 13.00 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
Vd (Volume of distribution) 0.49 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 8.70 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.03 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 0.79 hours Lombardo F, Berellini G, Obach RS

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 3.447 High 0.86
caco2-efflux Caco-2 efflux ratio (BA/AB) 0.374 High 0.86
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 52.966 10^-6 cm/s High 0.86
dh-clint Dog hepatocyte intrinsic clearance 133.968 uL/min/10^6 cells High 0.86
dppb Dog plasma protein binding (% unbound) 17.020 % High 0.86
fcs-ppb Fetal calf serum protein binding (% unbound) 32.070 % High 0.86
herg hERG pIC50 4.851 pIC50 High 0.86
hh-clint Human hepatocyte intrinsic clearance 31.117 uL/min/10^6 cells High 0.86
hlm-clint Human liver microsomal intrinsic clearance 215.278 uL/min/mg protein High 0.86
hppb Human plasma protein binding (% unbound) 11.740 % High 0.86
kinase-safety-class ACVR2B,AXL,BRAF,CAMK2B,CAMK2D,CDK5,CDK9,DDR1,EIF2AK3,EPHB4,ERBB2,GRK2,MAPK7,MAPKAPK2,NTRK2,PDK2,PDK4,PIK3CB,PRKDC,SIK2,SIK3,TEK 22
kinase-selectivity-class AXL,BRAF,DDR1,EPHB4,ERBB2,GRK2,MAPK7,PDK4,SIK2,SIK3 10
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 0.551 High 0.86
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 0.328 High 0.86
mh-clint Mouse hepatocyte intrinsic clearance 319.890 High 0.86
mppb Mouse plasma protein binding (% unbound) 24.490 High 0.86
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 0.752 High 0.86
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pld-class Phospholipidosis risk class (1 = positive, 0 = negative) 0 High 1
pppb Pig plasma protein binding (% unbound) 33.850 % High 0.86
rat-kpuu-brain Rat brain Kpuu 1.426 % High 0.86
rh-clint Rat hepatocyte intrinsic clearance 286.418 uL/min/10^6 cells High 0.86
rh-fuinc Rat hepatocyte fraction unbound in incubation 76.230 % High 0.86
rppb Rat plasma protein binding (% unbound) 16.860 % High 0.86
solubility-dd Solubility at pH 7.4 in DMSO 501.187 uM High 0.86

Approvals:

DateAgencyCompanyOrphan
Aug. 5, 1999 FDA PURDUE PHARMA LP

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
Mental status changes postoperative 66.39 50.82 9 944 189 90627305
Acute generalised exanthematous pustulosis 64.39 50.82 17 936 13686 90613808
Confusion postoperative 64.26 50.82 9 944 242 90627252
Maternal exposure during delivery 62.18 50.82 13 940 3833 90623661
Foetal exposure during delivery 52.85 50.82 8 945 372 90627122
Anaphylactic reaction 52.20 50.82 23 930 87501 90539993

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
Anaphylactic reaction 62.88 52.87 18 194 42725 42578398

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
Anaphylactic reaction 109.00 39.22 42 1126 114258 110473873
Maternal exposure during delivery 63.09 39.22 13 1155 3552 110584579
Mental status changes postoperative 57.59 39.22 8 1160 201 110587930
Acute generalised exanthematous pustulosis 56.59 39.22 17 1151 21647 110566484
Confusion postoperative 53.07 39.22 8 1160 360 110587771
Cauda equina syndrome 51.07 39.22 10 1158 2112 110586019
Anaphylactic shock 45.65 39.22 18 1150 51528 110536603
Injection site calcification 42.72 39.22 5 1163 29 110588102
Hypotension 39.27 39.22 37 1131 523812 110064319

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC N01BB10 NERVOUS SYSTEM
ANESTHETICS
ANESTHETICS, LOCAL
Amides
MeSH PA D000777 Anesthetics
MeSH PA D000779 Anesthetics, Local
MeSH PA D002492 Central Nervous System Depressants
MeSH PA D018689 Sensory System Agents
CHEBI has role CHEBI:35480 analgesic
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:36333 local anaesthetic
CHEBI has role CHEBI:37733 EC 3.1.1.8 (cholinesterase) inhibitor
CHEBI has role CHEBI:37887 adrenergic antagonist
CHEBI has role CHEBI:59941 amphiphile
CHEBI has role CHEBI:60186 EC 3.6.3.8 (<em>Ca</em><small><sup>2+</small></sup>-transporting ATPase) inhibitor

Related Drugs by ATC class:

N01BB Amides 10 drugs
articainebupivacainebutanilicainecinchocaineetidocainelidocainemeloxicammepivacaineprilocaineropivacaine

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

DiseaseRelationSNOMED_IDDOID
Anesthesia for cesarean section indication 4847005
Local anesthesia indication 386761002
Regional Anesthesia for Surgery indication
Regional Anesthesia for Labor Pain indication
Major Nerve Block for Surgery indication
Regional Anesthesia for Postoperative Pain indication
Disorder of cardiovascular system contraindication 49601007 DOID:1287
Kidney disease contraindication 90708001 DOID:557
Myasthenia gravis contraindication 91637004 DOID:437
Disease of liver contraindication 235856003 DOID:409
Deficiency of cholinesterase contraindication 360607009




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 13.24 acidic
pKa2 7.92 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
Sodium channel protein type 4 subunit alpha Ion channel BLOCKER WOMBAT-PK CHEMBL
Sodium channel protein type 1 subunit alpha Ion channel IC50 5.79 WOMBAT-PK
Prostaglandin E2 receptor EP1 subtype GPCR WOMBAT-PK
Cytochrome P450 2D6 Enzyme IC50 6.71 DRUG MATRIX
5-hydroxytryptamine receptor 3A Ion channel WOMBAT-PK
Potassium voltage-gated channel subfamily D member 3 Ion channel IC50 4.50 WOMBAT-PK
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 4.89 CHEMBL
Potassium voltage-gated channel subfamily A member 5 Ion channel WOMBAT-PK

External reference:

IDSource
4021287 VUID
N0000148724 NUI
D01287 KEGG_DRUG
259453 RXNORM
C0873118 UMLSCUI
CHEBI:6149 CHEBI
OJ0 PDB_CHEM_ID
CHEMBL1201193 ChEMBL_ID
DB01002 DRUGBANK_ID
CHEMBL1200749 ChEMBL_ID
D000077554 MESH_DESCRIPTOR_UI
92253 PUBCHEM_CID
7211 IUPHAR_LIGAND_ID
7465 INN_ID
27262-48-2 SECONDARY_CAS_RN
A5H73K9U3W UNII
8289 MMSL
d04449 MMSL
4021287 VANDF
4021288 VANDF
008081 NDDF
008082 NDDF
116103003 SNOMEDCT_US
387011006 SNOMEDCT_US
412237003 SNOMEDCT_US

Pharmaceutical products:

None