nalbuphine ๐Ÿถ Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
opioid receptor antagonists/agonists related to normorphine 1874 20594-83-6

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • nalbuphine
  • N-Cyclobutylmethyl-14-hydroxydihydronormorphine
  • nalbuphine hydrochloride
  • nalbuphine HCl
A narcotic used as a pain medication. It appears to be an agonist at KAPPA RECEPTORS and an antagonist or partial agonist at MU RECEPTORS.
  • Molecular weight: 357.45
  • Formula: C21H27NO4
  • CLOGP: 1.05
  • LIPINSKI: 0
  • HAC: 5
  • HDO: 3
  • TPSA: 73.16
  • ALOGS: -2.23
  • ROTB: 2
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
80 mg P

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 35.50 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 4 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 2.80 ยตM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 16 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 4.60 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 22 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.50 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 3.70 hours Lombardo F, Berellini G, Obach RS

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 1.948 Moderate 0.65
caco2-efflux Caco-2 efflux ratio (BA/AB) 2.455 Moderate 0.65
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 16.711 10^-6 cm/s Moderate 0.65
dh-clint Dog hepatocyte intrinsic clearance 18.239 uL/min/10^6 cells Moderate 0.65
dppb Dog plasma protein binding (% unbound) 40.840 % Moderate 0.65
fcs-ppb Fetal calf serum protein binding (% unbound) 68.530 % Moderate 0.65
herg hERG pIC50 4.870 pIC50 Moderate 0.65
hh-clint Human hepatocyte intrinsic clearance 7.261 uL/min/10^6 cells Moderate 0.65
hlm-clint Human liver microsomal intrinsic clearance 27.669 uL/min/mg protein Moderate 0.65
hppb Human plasma protein binding (% unbound) 49.310 % Moderate 0.65
kinase-safety-class ACVR2B,BRAF,BTK,CAMK2D,CDK5,EIF2AK3,ERBB2,GRK2,ITK,MAP2K6,MAPK10,MAPK7,NTRK2,PDK1,PDK2,PDK4,PRKDC,TEK,TGFBR1 19
kinase-selectivity-class EIF2AK3,MAP2K6,MAP3K14 3
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 3.251 Moderate 0.65
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 4.732 Moderate 0.65
mh-clint Mouse hepatocyte intrinsic clearance 62.373 Moderate 0.65
mppb Mouse plasma protein binding (% unbound) 51.090 Moderate 0.65
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 17.701 Moderate 0.65
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pld-class Phospholipidosis risk class (1 = positive, 0 = negative) 0 Moderate 0.65
pppb Pig plasma protein binding (% unbound) 68.880 % Moderate 0.65
rat-kpuu-brain Rat brain Kpuu 0.058 % Moderate 0.65
rh-clint Rat hepatocyte intrinsic clearance 87.096 uL/min/10^6 cells Moderate 0.65
rh-fuinc Rat hepatocyte fraction unbound in incubation 79.360 % Moderate 0.65
rppb Rat plasma protein binding (% unbound) 37.060 % Moderate 0.65
solubility-dd Solubility at pH 7.4 in DMSO 916.220 uM Moderate 0.65

Approvals:

DateAgencyCompanyOrphan
May 15, 1979 FDA

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 hypersensitivity 229.99 46.27 93 535 463516 90164303
Pancreatitis acute 93.76 46.27 25 603 32090 90595729
Antithrombin III 89.85 46.27 11 617 156 90627663

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
Neonatal epileptic seizure 63.84 42.43 8 601 63 42620663
Neonatal asphyxia 48.62 42.43 8 601 468 42620258
Febrile bone marrow aplasia 45.69 42.43 13 596 10168 42610558

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
Drug hypersensitivity 142.93 38.08 76 1062 454014 110134147
Pancreatitis acute 95.25 38.08 32 1106 60242 110527919
Febrile bone marrow aplasia 47.24 38.08 14 1124 17451 110570710
Antithrombin III 46.48 38.08 6 1132 87 110588074
Transverse sinus thrombosis 40.44 38.08 7 1131 771 110587390

FDA Adverse Event Reporting System (Pediatric)

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
Neonatal epileptic seizure 43.78 38.70 8 16 63 113866

Pharmacologic Action:

SourceCodeDescription
ATC N02AF02 NERVOUS SYSTEM
ANALGESICS
OPIOIDS
Morphinan derivatives
MeSH PA D000700 Analgesics
MeSH PA D000701 Analgesics, Opioid
MeSH PA D002492 Central Nervous System Depressants
MeSH PA D009294 Narcotics
MeSH PA D018689 Sensory System Agents
FDA MoA N0000175685 Partial Opioid Agonists
FDA MoA N0000175686 Competitive Opioid Antagonists
FDA EPC N0000175692 Opioid Agonist/Antagonist
CHEBI has role CHEBI:35482 opioid analgesic
CHEBI has role CHEBI:50137 ฮผ-opioid receptor antagonist

Related Drugs by ATC class:

N02AF Morphinan derivatives 1 drug
butorphanol

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

DiseaseRelationSNOMED_IDDOID
Pain indication 22253000
General anesthesia indication 50697003
Labor pain indication 247412007
Local anesthesia indication 386761002
Suicidal thoughts contraindication 6471006
Dependent drug abuse contraindication 6525002
Alcohol withdrawal delirium contraindication 8635005
Asthenia contraindication 13791008
Constipation contraindication 14760008 DOID:2089
Mood swings contraindication 18963009
Inflammatory bowel disease contraindication 24526004 DOID:0050589
Alcohol intoxication contraindication 25702006
Shock contraindication 27942005
Hypercapnia contraindication 29596007
Dehydration contraindication 34095006
Disorder of gallbladder contraindication 39621005 DOID:0060262
Hypothyroidism contraindication 40930008 DOID:1459
Conduction disorder of the heart contraindication 44808001
Low blood pressure contraindication 45007003
Bradycardia contraindication 48867003
Ulcerative colitis contraindication 64766004 DOID:8577
Substance abuse contraindication 66214007
Benign intracranial hypertension contraindication 68267002 DOID:11459
Urethral stricture contraindication 76618002
Decreased respiratory function contraindication 80954004
Injury of head contraindication 82271004
Cor pulmonale contraindication 83291003 DOID:8515
Pulmonary emphysema contraindication 87433001
Kidney disease contraindication 90708001 DOID:557
Acute abdominal pain contraindication 116290004
Neoplasm of brain contraindication 126952004 DOID:1319
Seizure disorder contraindication 128613002
Drug-induced psychosis contraindication 191483003 DOID:1742
Disease of liver contraindication 235856003 DOID:409
Morbid obesity contraindication 238136002 DOID:11981
Benign prostatic hyperplasia contraindication 266569009
Retention of urine contraindication 267064002
Exacerbation of asthma contraindication 281239006
Lesion of brain contraindication 301766008
Coma contraindication 371632003
Primary adrenocortical insufficiency contraindication 373662000
Operation on gastrointestinal tract contraindication 386621005
Hypoxia contraindication 389086002
Central nervous system depression contraindication 418072004
Dysfunction of sphincter of Oddi contraindication 430887001




๐Ÿถ Veterinary Drug Use

None

๐Ÿถ Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.93 acidic
pKa2 8.23 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
Mu-type opioid receptor GPCR AGONIST Ki 8.80 WOMBAT-PK CHEMBL
Kappa-type opioid receptor GPCR AGONIST Ki 8 WOMBAT-PK CHEMBL
Delta-type opioid receptor GPCR AGONIST Ki 6 WOMBAT-PK CHEMBL
Kappa-type opioid receptor GPCR AGONIST IC50 7.40 IUPHAR

External reference:

IDSource
4019851 VUID
N0000147937 NUI
D00843 KEGG_DRUG
23277-43-2 SECONDARY_CAS_RN
4019046 VANDF
4019851 VANDF
C0027348 UMLSCUI
CHEBI:7454 CHEBI
CHEMBL895 ChEMBL_ID
DB00844 DRUGBANK_ID
CHEMBL1201132 ChEMBL_ID
D009266 MESH_DESCRIPTOR_UI
5311304 PUBCHEM_CID
1663 IUPHAR_LIGAND_ID
2623 INN_ID
L2T84IQI2K UNII
154985 RXNORM
2038 MMSL
5147 MMSL
d00839 MMSL
001565 NDDF
004627 NDDF
111123003 SNOMEDCT_US
373539006 SNOMEDCT_US
83085007 SNOMEDCT_US
L2T84IQI2K INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Nalbuphine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0404-9766 INJECTION 20 mg INTRAMUSCULAR ANDA 14 sections
Nalbuphine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0404-9767 INJECTION 10 mg INTRAMUSCULAR ANDA 14 sections
Nalbuphine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0404-9917 INJECTION, SOLUTION 20 mg INTRAMUSCULAR ANDA 14 sections
Nalbuphine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0404-9918 INJECTION, SOLUTION 10 mg INTRAMUSCULAR ANDA 14 sections
Nalbuphine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0404-9919 INJECTION, SOLUTION 10 mg INTRAVENOUS ANDA 14 sections
Nalbuphine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0409-1463 INJECTION, SOLUTION 10 mg INTRAMUSCULAR ANDA 27 sections
Nalbuphine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0409-1463 INJECTION, SOLUTION 10 mg INTRAMUSCULAR ANDA 27 sections
Nalbuphine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0409-1464 INJECTION, SOLUTION 10 mg INTRAMUSCULAR ANDA 27 sections
Nalbuphine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0409-1465 INJECTION, SOLUTION 20 mg INTRAMUSCULAR ANDA 27 sections
Nalbuphine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0409-1467 INJECTION, SOLUTION 20 mg INTRAMUSCULAR ANDA 27 sections
NALBUPHINE HCI HUMAN PRESCRIPTION DRUG LABEL 1 51662-1418 INJECTION, SOLUTION 20 mg INTRAMUSCULAR ANDA 14 sections
NALBUPHINE HCI HUMAN PRESCRIPTION DRUG LABEL 1 51662-1420 INJECTION, SOLUTION 10 mg INTRAVENOUS ANDA 14 sections
Nalbuphine hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 70069-661 INJECTION 10 mg INTRAMUSCULAR ANDA 13 sections
Nalbuphine hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 70069-662 INJECTION 20 mg INTRAMUSCULAR ANDA 13 sections
Nalbuphine hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 70069-671 INJECTION 10 mg INTRAMUSCULAR ANDA 13 sections
Nalbuphine hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 70069-672 INJECTION 20 mg INTRAMUSCULAR ANDA 13 sections
Nalbuphine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 71872-7114 INJECTION, SOLUTION 10 mg INTRAMUSCULAR ANDA 29 sections
Nalbuphine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 71872-7320 INJECTION, SOLUTION 20 mg INTRAVENOUS ANDA 27 sections
Nalbuphine hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 71872-7331 INJECTION 10 mg INTRAVENOUS ANDA 13 sections
Nalbuphine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 84549-464 INJECTION, SOLUTION 10 mg INTRAMUSCULAR ANDA 27 sections