Welcome to DrugBank 4.0! If you prefer, you can still go back to version 3.0.
Identification
NameBupivacaine
Accession NumberDB00297  (APRD00247)
Typesmall molecule
Groupsapproved, investigational
Description

A widely used local anesthetic agent. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
(+-)-BupivacaineNot AvailableNot Available
1-Butyl-2',6'-pipecoloxylidideNot AvailableNot Available
1-Butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamideNot AvailableNot Available
BupivacainaSpanishINN
BupivacainumLatinINN
CarbostesinNot AvailableNot Available
dl-1-Butyl-2',6'-pipecoloxylidideNot AvailableNot Available
DL-BupivacaineNot AvailableNot Available
Salts
Name/CAS Structure Properties
Bupivacaine Hydrochloride
14252-80-3
Thumb
  • InChI Key: SIEYLFHKZGLBNX-UHFFFAOYNA-N
  • Monoisotopic Mass: 324.196841267
  • Average Mass: 324.889
DBSALT000202
Brand names
NameCompany
BupivanSun
CarbostesinAstraZeneca
MarcainAstraZeneca
MarcainaAstraZeneca
MarcaineCareStream Dental
SensorcaineAstra Zeneca
Sensorcaine-MPFAstra Zeneca
VivacaineSeptodont
Brand mixtures
Brand NameIngredients
Marcaine EBupivacaine Hydrochloride + Epinephrine Bitartrate
Sensorcaine ForteBupivacaine Hydrochloride + Epinephrine Bitartrate
Categories
CAS number2180-92-9
WeightAverage: 288.4277
Monoisotopic: 288.220163528
Chemical FormulaC18H28N2O
InChI KeyInChIKey=LEBVLXFERQHONN-UHFFFAOYSA-N
InChI
InChI=1S/C18H28N2O/c1-4-5-12-20-13-7-6-11-16(20)18(21)19-17-14(2)9-8-10-15(17)3/h8-10,16H,4-7,11-13H2,1-3H3,(H,19,21)
IUPAC Name
1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide
SMILES
CCCCN1CCCCC1C(=O)NC1=C(C)C=CC=C1C
Mass Specshow(8.44 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids and Derivatives
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentAlpha Amino Acid Amides
Alternative parentsAnilides; Piperidinecarboxylic Acids; Toluenes; Secondary Carboxylic Acid Amides; Tertiary Amines; Enolates; Carboxylic Acids; Polyamines
Substituentsacetanilide; piperidinecarboxylic acid; toluene; piperidine; benzene; carboxamide group; secondary carboxylic acid amide; tertiary amine; polyamine; carboxylic acid; enolate; amine; organonitrogen compound
Classification descriptionThis compound belongs to the alpha amino acid amides. These are amide derivatives of alpha amino acids.
Pharmacology
IndicationFor the production of local or regional anesthesia or analgesia for surgery, for oral surgery procedures, for diagnostic and therapeutic procedures, and for obstetrical procedures.
PharmacodynamicsBupivacaine is a widely used local anesthetic agent. Bupivacaine is often administered by spinal injection prior to total hip arthroplasty. It is also commonly injected into surgical wound sites to reduce pain for up to 20 hours after surgery. In comparison to other local anesthetics it has a long duration of action. It is also the most toxic to the heart when administered in large doses. This problem has led to the use of other long-acting local anaesthetics:ropivacaine and levobupivacaine. Levobupivacaine is a derivative, specifically an enantiomer, of bupivacaine. Systemic absorption of local anesthetics produces effects on the cardiovascular and central nervous systems. At blood concentrations achieved with therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance are minimal. However, toxic blood concentrations depress cardiac conduction and excitability, which may lead to atrioventricular block, ventricular arrhythmias and to cardiac arrest, sometimes resulting in fatalities. In addition, myocardial contractility is depressed and peripheral vasodilation occurs, leading to decreased cardiac output and arterial blood pressure. Following systemic absorption, local anesthetics can produce central nervous system stimulation, depression or both.
Mechanism of actionLocal anesthetics such as bupivacaine block the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. Bupivacaine binds to the intracellular portion of sodium channels and blocks sodium influx into nerve cells, which prevents depolarization. In general, the progression of anesthesia is related to the diameter, myelination and conduction velocity of affected nerve fibers. Clinically, the order of loss of nerve function is as follows: (1) pain, (2) temperature, (3) touch, (4) proprioception, and (5) skeletal muscle tone. The analgesic effects of Bupivicaine are thought to potentially be due to its binding to the prostaglandin E2 receptors, subtype EP1 (PGE2EP1), which inhibits the production of prostaglandins, thereby reducing fever, inflammation, and hyperalgesia.
AbsorptionThe rate of systemic absorption of local anesthetics is dependent upon the total dose and concentration of drug administered, the route of administration, the vascularity of the administration site, and the presence or absence of epinephrine in the anesthetic solution.
Volume of distributionNot Available
Protein binding95%
Metabolism

Amide-type local anesthetics such as bupivacaine are metabolized primarily in the liver via conjugation with glucuronic acid. The major metabolite of bupivacaine is 2,6-pipecoloxylidine, which is mainly catalyzed via cytochrome P450 3A4.

SubstrateEnzymesProduct
Bupivacaine
    2,6-pipecoloxylidineDetails
    Route of eliminationOnly 6% of bupivacaine is excreted unchanged in the urine.
    Half life2.7 hours in adults and 8.1 hours in neonates
    ClearanceNot Available
    ToxicityThe mean seizure dosage of bupivacaine in rhesus monkeys was found to be 4.4 mg/kg with mean arterial plasma concentration of 4.5 mcg/mL. The intravenous and subcutaneous LD 50 in mice is 6 to 8 mg/kg and 38 to 54 mg/kg respectively. Recent clinical data from patients experiencing local anesthetic induced convulsions demonstrated rapid development of hypoxia, hypercarbia, and acidosis with bupivacaine within a minute of the onset of convulsions. These observations suggest that oxygen consumption and carbon dioxide production are greatly increased during local anesthetic convulsions and emphasize the importance of immediate and effective ventilation with oxygen which may avoid cardiac arrest.
    Affected organisms
    • Humans and other mammals
    Pathways
    PathwayCategorySMPDB ID
    Bupivacaine Action PathwayDrug actionSMP00393
    SNP Mediated EffectsNot Available
    SNP Mediated Adverse Drug ReactionsNot Available
    ADMET
    Predicted ADMET features
    Property Value Probability
    Human Intestinal Absorption + 0.9814
    Blood Brain Barrier + 0.936
    Caco-2 permeable + 0.6669
    P-glycoprotein substrate Substrate 0.8435
    P-glycoprotein inhibitor I Inhibitor 0.8582
    P-glycoprotein inhibitor II Non-inhibitor 0.7836
    Renal organic cation transporter Non-inhibitor 0.6471
    CYP450 2C9 substrate Non-substrate 0.7957
    CYP450 2D6 substrate Substrate 0.8346
    CYP450 3A4 substrate Substrate 0.7045
    CYP450 1A2 substrate Inhibitor 0.6863
    CYP450 2C9 substrate Non-inhibitor 0.9099
    CYP450 2D6 substrate Inhibitor 0.8932
    CYP450 2C19 substrate Non-inhibitor 0.9026
    CYP450 3A4 substrate Inhibitor 0.6205
    CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6066
    Ames test Non AMES toxic 0.8462
    Carcinogenicity Non-carcinogens 0.8859
    Biodegradation Not ready biodegradable 0.9729
    Rat acute toxicity 2.2574 LD50, mol/kg Not applicable
    hERG inhibition (predictor I) Weak inhibitor 0.8283
    hERG inhibition (predictor II) Inhibitor 0.7851
    Pharmacoeconomics
    Manufacturers
    • Hospira inc
    • International medicated systems ltd
    • App pharmaceuticals llc
    Packagers
    Dosage forms
    FormRouteStrength
    LiquidInfiltration
    SolutionEpidural
    SolutionInfiltration
    SolutionIntraspinal
    Prices
    Unit descriptionCostUnit
    Bupivacaine hcl powder18.36USDg
    Sensorcaine-dextr 0.75% amp2.36USDml
    Marcaine spinal ampul0.93USDml
    Bupivacaine 0.5% on-q pump0.63USDml
    Bupivacaine hcl 0.5% on-q pump0.63USDml
    Bupivacaine 0.25% on-q pump0.62USDml
    Marcaine 0.25% vial0.26USDml
    Bupivacaine hcl-ns 0.0625%0.25USDml
    Bupivacaine-ns 0.1% on-q pump0.25USDml
    Sensorcaine 0.25% vial0.2USDml
    Bupivacaine hcl-ns 0.1%0.17USDml
    Bupivacaine hcl-ns 0.2%0.15USDml
    Bupivacaine 0.25% vial0.11USDml
    Bupivacaine 0.25% ampul0.1USDml
    Bupivacaine hcl-ns 0.125% bag0.1USDml
    Bupivacaine hcl-ns 0.25%0.1USDml
    DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
    PatentsNot Available
    Properties
    Statesolid
    Experimental Properties
    PropertyValueSource
    melting point107-108 °CPhysProp
    water solubility2400 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
    logP3.41HANSCH,C ET AL. (1995)
    pKa8.1Not Available
    Predicted Properties
    PropertyValueSource
    water solubility9.77e-02 g/lALOGPS
    logP3.31ALOGPS
    logP4.52ChemAxon
    logS-3.5ALOGPS
    pKa (strongest acidic)13.62ChemAxon
    pKa (strongest basic)8ChemAxon
    physiological charge1ChemAxon
    hydrogen acceptor count2ChemAxon
    hydrogen donor count1ChemAxon
    polar surface area32.34ChemAxon
    rotatable bond count5ChemAxon
    refractivity90.19ChemAxon
    polarizability34.19ChemAxon
    number of rings2ChemAxon
    bioavailability1ChemAxon
    rule of fiveYesChemAxon
    Ghose filterYesChemAxon
    Veber's ruleYesChemAxon
    MDDR-like ruleNoChemAxon
    Spectra
    SpectraNot Available
    References
    Synthesis Reference

    Thuresson, B. and Egner, B.P.H.; U.S. Patent 2,792,399; May 14, 1957; assigned to AB Bofors, Sweden.
    Thuresson, B. and Pettersson, B.G.; US. Patent 2,955.1 11; October 4,1960; assigned to AB
    Bofors, Sweden.

    US2955111
    General Reference
    1. Link
    2. Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, Eisenkraft JB: Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology. 2006 Jul;105(1):217-8. Pubmed
    3. Picard J, Meek T: Lipid emulsion to treat overdose of local anaesthetic: the gift of the glob. Anaesthesia. 2006 Feb;61(2):107-9. Pubmed
    External Links
    ResourceLink
    KEGG CompoundC07529
    PubChem Compound2474
    PubChem Substance46506768
    ChemSpider2380
    ChEBI3215
    ChEMBLCHEMBL1098
    Therapeutic Targets DatabaseDAP001229
    PharmGKBPA135057240
    IUPHAR2397
    Guide to Pharmacology2397
    Drug Product Database2165414
    RxListhttp://www.rxlist.com/cgi/generic2/bupivacaine.htm
    Drugs.comhttp://www.drugs.com/cdi/bupivacaine-solution.html
    WikipediaBupivacaine
    ATC CodesN01BB01N01BB10
    AHFS Codes
    • 72:00.00
    PDB EntriesNot Available
    FDA labelshow(147 KB)
    MSDSshow(73.3 KB)
    Interactions
    Drug Interactions
    Drug
    ConivaptanConivaptan may increase the serum concentration of CYP3A4 Substrates such as bupivacaine. Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates.
    Food InteractionsNot Available

    1. Sodium channel protein type 10 subunit alpha

    Kind: protein

    Organism: Human

    Pharmacological action: yes

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Sodium channel protein type 10 subunit alpha Q9Y5Y9 Details

    References:

    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
    3. Sheets MF, Fozzard HA, Lipkind GM, Hanck DA: Sodium channel molecular conformations and antiarrhythmic drug affinity. Trends Cardiovasc Med. 2010 Jan;20(1):16-21. Pubmed

    2. Prostaglandin E2 receptor EP1 subtype

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: other/unknown

    Components

    Name UniProt ID Details
    Prostaglandin E2 receptor EP1 subtype P34995 Details

    References:

    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
    3. Beloeil H, Gentili M, Benhamou D, Mazoit JX: The effect of a peripheral block on inflammation-induced prostaglandin E2 and cyclooxygenase expression in rats. Anesth Analg. 2009 Sep;109(3):943-50. Pubmed

    1. Cytochrome P450 3A4

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate

    Components

    Name UniProt ID Details
    Cytochrome P450 3A4 P08684 Details

    References:

    1. Gantenbein M, Attolini L, Bruguerolle B, Villard PH, Puyoou F, Durand A, Lacarelle B, Hardwigsen J, Le-Treut YP: Oxidative metabolism of bupivacaine into pipecolylxylidine in humans is mainly catalyzed by CYP3A. Drug Metab Dispos. 2000 Apr;28(4):383-5. Pubmed
    2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

    2. Cytochrome P450 1A2

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate

    Components

    Name UniProt ID Details
    Cytochrome P450 1A2 P05177 Details

    References:

    1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

    3. Cytochrome P450 2C19

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate

    Components

    Name UniProt ID Details
    Cytochrome P450 2C19 P33261 Details

    References:

    1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

    4. Cytochrome P450 2D6

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate

    Components

    Name UniProt ID Details
    Cytochrome P450 2D6 P10635 Details

    References:

    1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

    Comments
    Drug created on June 13, 2005 07:24 / Updated on April 02, 2014 10:14