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Drug

D0016 | Bupivacaine

Molecular Formula C18H28N2O
Molecular Weight 288.4
Structure
State solid
Route of elimination Only 6% of bupivacaine is excreted unchanged in the urine.
Protein binding 0.95
Half life 2.7 hours in adults and 8.1 hours in neonates
Absorption Systemic absorption of local anesthetics is dose- and concentration-dependendent on the total drug administered. Other factors that affect the rate of systemic absorption include the route of administration, blood flow at the administration site, and the presence or absence of epinephrine in the anesthetic solution.
Description local anesthetic agent

N

N01BB51 Bupivacaine, combinations


[N01BB] Amides


[N01B] ANESTHETICS, LOCAL


[N01] ANESTHETICS


[N] Nervous system

N01BB01 Bupivacaine


[N01BB] Amides


[N01B] ANESTHETICS, LOCAL


[N01] ANESTHETICS


[N] Nervous system

Toxicity Dose Time Species Model Method Action Positive criterion Reference
DEPOLARIZATION decrease 61
OPENING OF PERMEABILITY TRANSITION PORE (PTP) decrease 61
UNCOUPLING rat isolated liver mitochondria measurements of mitochondrial respiration; RST inhibition assay, RST uncoupling assay; IC 50ratio of glucose/galactose assay Negative 53
ELECTROPHORETIC UNCOUPLING 278
MEMBRANE POTENTIAL 258.2 µM 30 mins mouse liver mitochondria Rh123 fluorescence (excitation 485 nm, emission 535 nm) are recorded using a fluorescence multi-well plate reader (mCICCP (20 µM) treatments was considered as the 100% baseline for ΔΨm loss) decrease EC20 36
RESPIRATION decrease 61
RESPIRATION 60.6 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition. decrease EC20 36
RESPIRATION > 800 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition. decrease EC20 36
ELECTRON TRANSPORT CHAIN rat isolated liver mitochondria measurements of mitochondrial respiration; RST inhibition assay, RST uncoupling assay; IC 50ratio of glucose/galactose assay Negative 53
SWELLING > 800 µM 30 mins mouse liver mitochondria swelling assay: Absorbance at 545 nm using a fluorescence multi-well plate reader (CaCl2 (50 µM) was considered as the 100% baseline for the swelling ) increase EC20 36

Target Dose Time Species Model Method Action Positive criterion Reference
NADH:ubiquinone reductase 60.6 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition. inhibit EC20 36
Succinate dehydrogenase > 800 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition. inhibit EC20 36
Cytochrome c > 800 µM 30 mins mouse liver mitochondria Cytochrome c release was evaluated using ELISA kit ( 20 µg/ml Alamethicin was used as 100% baseline) release EC20 36

Pictogram Signal Statements Precautionary Statement Codes
Danger

The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.


H300 (100%): Fatal if swallowed [Danger Acute toxicity, oral]


H310 (100%): Fatal in contact with skin [Danger Acute toxicity, dermal]


H330 (100%): Fatal if inhaled [Danger Acute toxicity, inhalation]


 P260, P262, P264, P270, P271, P280, P284, P301+P310, P302+P350, P304+P340, P310, P320, P321, P322, P330, P361, P363, P403+P233, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)
Danger

The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.


H300 (100%): Fatal if swallowed [Danger Acute toxicity, oral]


H310 (100%): Fatal in contact with skin [Danger Acute toxicity, dermal]


H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]


H318 (100%): Causes serious eye damage [Danger Serious eye damage/eye irritation]


H330 (100%): Fatal if inhaled [Danger Acute toxicity, inhalation]


 P260, P262, P264, P270, P271, P280, P284, P301+P310, P302+P350, P302+P352, P304+P340, P305+P351+P338, P310, P320, P321, P322, P330, P332+P313, P361, P362, P363, P403+P233, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)

Organism Test type Route Dose (normalized dose) Effect Source
rabbit LD50 intratracheal 12500ug/kg (12.5mg/kg) Arzneimittel-Forschung. Drug Research. Vol. 26, Pg. 78, 1976.
rabbit LD50 oral 18mg/kg (18mg/kg) Archives Internationales de Pharmacodynamie et de Therapie. Vol. 200, Pg. 359, 1972.
rabbit LD50 intratracheal 11mg/kg (11mg/kg) Archives Internationales de Pharmacodynamie et de Therapie. Vol. 200, Pg. 359, 1972.
mouse LD50 intravenous 7100ug/kg (7.1mg/kg) United States Patent Document. Vol. #3632766,
rabbit LD50 parenteral 64mg/kg (64mg/kg) Arzneimittel-Forschung. Drug Research. Vol. 26, Pg. 78, 1976.
rat LD50 subcutaneous 52mg/kg (52mg/kg) Acta Pharmacologica et Toxicologica. Vol. 31, Pg. 273, 1972.
mouse LD50 subcutaneous 100mg/kg (100mg/kg) Acta Pharmacologica et Toxicologica. Vol. 31, Pg. 273, 1972.
rabbit LD50 intravenous 1620ug/kg (1.62mg/kg) Anesthesia and Analgesia Vol. 64, Pg. 209, 1985.
mouse LD50 intravenous 9600ug/kg (9.6mg/kg) Acta Pharmacologica et Toxicologica. Vol. 31, Pg. 273, 1972.
guinea pig LD50 intraperitoneal 50mg/kg (50mg/kg) Drugs in Japan Vol. 6, Pg. 680, 1982.
rabbit LD50 intratracheal 14mg/kg (14mg/kg) Arzneimittel-Forschung. Drug Research. Vol. 26, Pg. 78, 1976.
rat LD50 intravenous 7200ug/kg (7.2mg/kg) Acta Pharmacologica et Toxicologica. Vol. 31, Pg. 273, 1972.
rabbit LDLo intravenous 9700ug/kg (9.7mg/kg) behavioral: convulsions or effect on seizure threshold Acta Pharmacologica et Toxicologica. Vol. 31, Pg. 273, 1972.
rat LD50 parenteral 30mg/kg (30mg/kg) Anesthesiology. Vol. 89, Pg. 1199, 1998.
rat LD50 intravenous 6mg/kg (6mg/kg) Archives Internationales de Pharmacodynamie et de Therapie. Vol. 200, Pg. 359, 1972.
mouse LD50 intramuscular 22753ug/kg (22.753mg/kg) Drug Development Research. Vol. 21, Pg. 277, 1990.
mouse LD50 subcutaneous 59mg/kg (59mg/kg) Archives Internationales de Pharmacodynamie et de Therapie. Vol. 200, Pg. 359, 1972.
rat LD50 subcutaneous 43mg/kg (43mg/kg) Archives Internationales de Pharmacodynamie et de Therapie. Vol. 200, Pg. 359, 1972.
mouse LD50 intravenous 6100ug/kg (6.1mg/kg) Anesthesia Progress. Vol. 36, Pg. 79, 1989.
rabbit LD50 parenteral 48mg/kg (48mg/kg) Archives Internationales de Pharmacodynamie et de Therapie. Vol. 200, Pg. 359, 1972.
rat LD50 subcutaneous 47mg/kg (47mg/kg) United States Patent Document. Vol. #3632766,
rabbit LD50 parenteral > 120mg/kg (120mg/kg) Arzneimittel-Forschung. Drug Research. Vol. 26, Pg. 78, 1976.
domestic animals - goat/sheep LDLo intravenous 150mg/kg (150mg/kg) Anesthesia and Analgesia Vol. 86, Pg. 797, 1998.
mouse LD50 subcutaneous 35mg/kg (35mg/kg) United States Patent Document. Vol. #3632766,
guinea pig LD50 intraperitoneal 36600ug/kg (36.6mg/kg) United States Patent Document. Vol. #3632766,
human TDLo intravenous 4300ug/kg (4.3mg/kg) Acta Anaesthesiologica Scandinavica. Vol. 21, Pg. 521, 1977.
rabbit LD50 intravenous 3400ug/kg (3.4mg/kg) Archives Internationales de Pharmacodynamie et de Therapie. Vol. 200, Pg. 359, 1972.
rat LD50 intravenous 5600ug/kg (5.6mg/kg) Acta Pharmacologica et Toxicologica. Vol. 31, Pg. 273, 1972.
mouse LD50 intraperitoneal 58700ug/kg (58.7mg/kg) Anesthesia and Analgesia Vol. 60, Pg. 385, 1981.

  • Atrioventricular block

  • Cardiac arrest

  • Cardiac output decreased

  • Chills

  • Coma

  • Convulsion

  • Foetor hepaticus

  • Hepatocellular injury

  • Hypotonia

  • Labour pain

  • Liver disorder

  • Procedural pain

  • Respiratory arrest

  • Tremor

  • Vascular resistance systemic

  • Vasodilation procedure

  • Ventricular arrhythmia

  • Wound

  • Lethargy (0.013)

  • Abdominal distension

  • Abdominal pain

  • Alanine aminotransferase increased

  • Anaemia

  • Anal haemorrhage

  • Anxiety

  • Aspartate aminotransferase increased

  • Back pain

  • Blood creatinine increased

  • Body temperature decreased

  • Body temperature increased

  • Bradycardia

  • Breast pain

  • Chills

  • Constipation

  • Cough

  • Decreased appetite

  • Delayed delivery

  • Diarrhoea

  • Diplopia

  • Dizziness

  • Dyschezia

  • Dyspepsia

  • Electrocardiogram abnormal

  • Feeling hot

  • Flatulence

  • Foetal distress syndrome

  • Fungal infection

  • Gastrointestinal disorder

  • Gastrointestinal pain

  • Haematuria

  • Haemorrhage in pregnancy

  • Headache

  • Hypertension

  • Hypoaesthesia

  • Hypotension

  • Hypothermia

  • Infection

  • Infestation

  • Leukocytosis

  • Loss of consciousness

  • Malnutrition

  • Nausea

  • Nervous system disorder

  • Pain

  • Paraesthesia

  • Post procedural swelling

  • Procedural pain

  • Pruritus

  • Pruritus generalised

  • Purpura

  • Rectal discharge

  • Shock

  • Skin disorder

  • Somnolence

  • Syncope

  • Tachycardia

  • Urinary incontinence

  • Urinary tract infection

  • Urine abnormality

  • Urine analysis abnormal

  • Urine flow decreased

  • Vascular purpura

  • Vomiting

  • Wound secretion

    • (+-)-Bupivacaine (+/-)-Bupivacaine (.+/-.)-1-Butyl-2',6'-pipecoloxylidide
    (.+/-.)-Bupivacaine (1)-1-Butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide (RS)-bupivacaine
    (plusmn)-1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide 1-Butyl-2',6'-pipecoloxylidide 1-Butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide
    1-Butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboximidic acid 1-butyl-N-(2,6-dimethylphenyl)-piperidine-2-carboxamide 1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide
    14252-80-3 (HCl) 18010-40-7 (HCl) 180B929
    2',6'-Pipecoloxylidide, 1-butyl- 2-Piperidinecarboxamide, 1-butyl-N-(2,6-dimethylphenyl)- 2-Piperidinecarboxamide, 1-butyl-N-(2,6-dimethylphenyl)-, (+-)-
    2-Piperidinecarboxamide, 1-butyl-N-(2,6-dimethylphenyl)-, (.+/-.)- 2180-92-9 38396-39-3
    4CH-013994 73360-54-0 (HCl.H2O) AB00053674
    AB00053674-08 AB00053674-09 AB00053674_10
    AB00053674_11 AC-2096 AH 250
    AK-90074 AKOS001637202 AKOS016842516
    ANW-45984 API0007792 AX8041457
    Anekain BCP12242 BCP21825
    BDBM50350790 BPBio1_000298 BRD-A01636364-003-05-2
    BRD-A01636364-003-08-6 BS-5224 BSPBio_000270
    BSPBio_002607 Bloqueina Bucaine (TN)
    Bupivacaina Bupivacaina [INN-Spanish] Bupivacaine (USAN/INN)
    Bupivacaine Carbonate Bupivacaine HCL KIT Bupivacaine Monohydrochloride, Monohydrate
    Bupivacaine [INN:BAN] Bupivacaine [USAN:INN:BAN] Bupivacaine liposome injectable suspension
    Bupivacaine,hydrochloride Bupivacainum Bupivacainum [INN-Latin]
    C07529 C18H28N2O CHEBI:3215
    CHEBI:77431 CHEMBL1098 CS-W023182
    CTK8B4736 Carbostesin D07552
    DB-119016 DB00297 DL-Bupivacaine
    DTXSID2022703 DUR-843 DivK1c_000758
    EINECS 218-553-3 EINECS 253-911-2 Epitope ID:122662
    Exparel Exparel (TN) FT-0623286
    FT-0699781 GTPL2397 HMS2090F12
    HMS3428P06 HSDB 7790 IDI1_000758
    J10217 KBio1_000758 KBio2_002004
    KBio2_004572 KBio2_007140 KBio3_001827
    KBioGR_001516 KBioSS_002004 KS-00000ZRC
    L000695 LAC-43 LAC-43 (Salt/Mix)
    LEBVLXFERQHONN-UHFFFAOYSA-N LS-109841 LS-2222
    Levobupivacaine free base M-9606 MCULE-2286784276
    MFCD00941462 Marcaine Marcaine hydrochloride (Salt/Mix)
    Marcaine spinal (Salt/Mix) N-(2,6-dimethylphenyl)(1-butyl(2-piperidyl))carboxamide NCGC00178579-01
    NCGC00178579-02 NINDS_000758 Prestwick0_000305
    Prestwick1_000305 Prestwick2_000305 Prestwick3_000305
    Q-100271 Q422806 R962
    SBI-0051846.P002 SC-26838 SCHEMBL25438
    SKY 0402 SKY-0402 SKY0402
    SPBio_001558 SPBio_002489 ST065773
    ST2415271 STL484283 Sensorcaine
    Spectrum2_001589 Spectrum3_000974 Spectrum4_001098
    Spectrum5_001483 Spectrum_001524 TC-134729
    Win 11318 bupivacaine bupivacaine base
    cBupivacaine dl-1-Butyl-2',6'-pipecoloxylidide dl-1-Butyl-2,6-pipecoloxylidide
    racemic bupivacaine

    DrugBank Name Bupivacaine
    DrugBank DB00297
    CAS Number 119427-31-5, 14252-80-3, 2180-92-9, 27262-47-1, 38396-39-3, 4033-39-0, 474668-57-0
    PubChem Compound 2474
    KEGG Compound ID C07529
    KEGG Drug D07552
    PubChem.Substance 46506768
    ChEBI 77431
    PharmGKB PA135057240
    ChemSpider 2380
    BindingDB 50350790.0
    TTD DAP001229
    Wikipedia Bupivacaine
    DPD 2493

    1. Dykens et al. (2007)
    2. Chan et al. (2005)