Identification
- Summary
Levobupivacaine is a drug used for nerve block and anesthesia.
- Generic Name
- Levobupivacaine
- DrugBank Accession Number
- DB01002
- Background
Levobupivacaine is an amino-amide local anaesthetic drug belonging to the family of n-alkylsubstituted pipecoloxylidide. It is the S-enantiomer of bupivacaine. Levobupivacaine hydrochloride is commonly marketed by AstraZeneca under the trade name Chirocaine. In particular, the specific levobupivacaine enantiomer is a worthwhile pursuit because it demonstrates less vasodilation and possesses a greater length of action in comparison to bupivacaine. It is approximately 13 per cent less potent (by molarity) than racemic bupivacaine.Levobupivacaine is indicated for local anaesthesia including infiltration, nerve block, ophthalmic, epidural and intrathecal anaesthesia in adults; and infiltration analgesia in children. When administered appropriately, the occurrence of adverse effects is not anticipated much if at all. In general, the majority of potential adverse effects are predominantly associated with inappropriate administration methods that may cause systemic exposure and/or toxicity associated with overexposure to an anesthetic. Regardless, allergic reactions may also occur - although only rarely.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Levobupivacaine (DB01002)
- Weight
- Average: 288.4277
Monoisotopic: 288.220163528 - Chemical Formula
- C18H28N2O
- Synonyms
- (-)-bupivacaine
- (S)-1-butyl-2',6'-pipecoloxylidide
- (S)-bupivacaine
- L-(-)-1-Butyl-2',6'-pipecoloxylidide
- L-(−)-bupivacaine
- Levobupivacaína
- Levobupivacaine
Pharmacology
- Indication
For the production of local or regional anesthesia for surgery and obstetrics, and for post-operative pain management
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Pain •••••••••••• •••••••••• ••••••••• •••••••• - Associated Therapies
- Contraindications & Blackbox Warnings
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Levobupivacaine, a local anesthetic agent, is indicated for the production of local or regional anesthesia or analgesia for surgery, for oral surgery procedures, for diagnostic and therapeutic procedures, and for obstetrical procedures.
- Mechanism of action
Local anesthetics such as Levobupivacaine 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. In general, the progression of anesthesia is related to the diameter, myelination and conduction velocity of affected nerve fibers. Specifically, the drug binds to the intracellular portion of sodium channels and blocks sodium influx into nerve cells, which prevents depolarization.
Target Actions Organism ASodium channel protein type 10 subunit alpha inhibitorHumans - Absorption
The plasma concentration of levobupivacaine following therapeutic administration depends on dose and also on route of administration, because absorption from the site of administration is affected by the vascularity of the tissue. Peak levels in blood were reached approximately 30 minutes after epidural administration, and doses up to 150 mg resulted in mean Cmax levels of up to 1.2 µg/mL.
- Volume of distribution
66.91 ±18.23 L [after intravenous administration of 40 mg in healthy volunteers]
- Protein binding
>97%
- Metabolism
Levobupivacaine is extensively metabolized with no unchanged levobupivacaine detected in urine or feces. In vitro studies using [14 C] levobupivacaine showed that CYP3A4 isoform and CYP1A2 isoform mediate the metabolism of levobupivacaine to desbutyl levobupivacaine and 3-hydroxy levobupivacaine, respectively. In vivo, the 3-hydroxy levobupivacaine appears to undergo further transformation to glucuronide and sulfate conjugates. Metabolic inversion of levobupivacaine to R(+)-bupivacaine was not evident both in vitro and in vivo.
- Route of elimination
Following intravenous administration, recovery of the radiolabelled dose of levobupivacaine was essentially quantitative with a mean total of about 95% being recovered in urine and feces in 48 hours. Of this 95%, about 71% was in urine while 24% was in feces.
- Half-life
3.3 hours
- Clearance
39.06 ±13.29 L/h [after intravenous administration of 40 mg in healthy volunteers]
- Adverse Effects
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LD50: 5.1mg/kg in rabbit, intravenous; 18mg/kg in rabbit, oral; 207mg/kg in rabbit, parenteral; 63mg/kg in rat, subcutaneous (Archives Internationales de Pharmacodynamie et de Therapie. Vol. 200, Pg. 359, 1972.) Levobupivacaine appears to cause less myocardial depression than both bupivacaine and ropivacaine, despite being in higher concentrations.
- Pathways
Pathway Category Levobupivacaine Action Pathway Drug action - Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Levobupivacaine is combined with 1,2-Benzodiazepine. Abacavir Levobupivacaine may decrease the excretion rate of Abacavir which could result in a higher serum level. Abaloparatide The risk or severity of adverse effects can be increased when Levobupivacaine is combined with Abaloparatide. Abametapir The serum concentration of Levobupivacaine can be increased when it is combined with Abametapir. Abatacept The metabolism of Levobupivacaine can be increased when combined with Abatacept. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Levobupivacaine hydrochloride J998RDZ51I 27262-48-2 SIEYLFHKZGLBNX-NTISSMGPSA-N - International/Other Brands
- Chirocaine (Abbott Laboratories) / Novabupi
Categories
- ATC Codes
- N01BB10 — Levobupivacaine
- Drug Categories
- Amides
- Amines
- Anesthetics
- Anesthetics, Local
- Anilides
- Aniline Compounds
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- Hypotensive Agents
- Nervous System
- Neuraxial Anesthetics
- Peripheral Nervous System Agents
- Sensory System Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as piperidinecarboxamides. These are compounds containing a piperidine ring substituted with a carboxamide functional group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Piperidines
- Sub Class
- Piperidinecarboxylic acids and derivatives
- Direct Parent
- Piperidinecarboxamides
- Alternative Parents
- m-Xylenes / Trialkylamines / Propargyl-type 1,3-dipolar organic compounds / Carboximidic acids / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Hydrocarbon derivatives
- Substituents
- 2-piperidinecarboxamide / Amine / Aromatic heteromonocyclic compound / Azacycle / Benzenoid / Carboximidic acid / Carboximidic acid derivative / Hydrocarbon derivative / M-xylene / Monocyclic benzene moiety
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- 1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide (CHEBI:6149)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- A5H73K9U3W
- CAS number
- 27262-47-1
- InChI Key
- LEBVLXFERQHONN-INIZCTEOSA-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)/t16-/m0/s1
- IUPAC Name
- (2S)-1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide
- SMILES
- CCCCN1CCCC[C@H]1C(=O)NC1=C(C)C=CC=C1C
References
- Synthesis Reference
Hooshang Shahriari Zavareh, Graham Anthony Charles Frampton, "Process for preparing levobupivacaine and analogues thereof." U.S. Patent US5777124, issued February, 1985.
US5777124- General References
- Burlacu CL, Buggy DJ: Update on local anesthetics: focus on levobupivacaine. Ther Clin Risk Manag. 2008 Apr;4(2):381-92. [Article]
- Leone S, Di Cianni S, Casati A, Fanelli G: Pharmacology, toxicology, and clinical use of new long acting local anesthetics, ropivacaine and levobupivacaine. Acta Biomed. 2008 Aug;79(2):92-105. [Article]
- EMC Summary of Product Characteristics: Chirocaine (levobupivacaine hydrochloride) solution for injection [Link]
- External Links
- Human Metabolome Database
- HMDB0015137
- KEGG Drug
- D08116
- KEGG Compound
- C07887
- PubChem Compound
- 92253
- PubChem Substance
- 46505295
- ChemSpider
- 83289
- BindingDB
- 50417951
- 259453
- ChEBI
- 6149
- ChEMBL
- CHEMBL1201193
- ZINC
- ZINC000001530812
- Therapeutic Targets Database
- DAP001233
- PharmGKB
- PA164754741
- PDBe Ligand
- OJ0
- RxList
- RxList Drug Page
- Wikipedia
- Levobupivacaine
- PDB Entries
- 8i5b
- FDA label
- Download (2.72 MB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Bradycardia / Breast Tumor / Hypotension 1 4 Active Not Recruiting Treatment Inguinal Hernias / Spinal Anesthesia therapy 1 4 Completed Not Available Anaesthesia / Nerve Block / Orthopaedic Disorders 1 4 Completed Not Available Hallux Valgus (Bunions) / Surgery 1 4 Completed Not Available Pain 1
Pharmacoeconomics
- Manufacturers
- Purdue pharma lp
- Packagers
- Ben Venue Laboratories Inc.
- Purdue Pharma LP
- Dosage Forms
Form Route Strength Solution Epidural 7.5 mg Injection, solution Epidural 0.625 MG/ML Injection, solution Epidural 2.5 mg/ml Injection, solution Epidural 5 mg/ml Injection, solution Epidural 7.5 mg/ml Injection Epidural 2.5 MG/ML Solution Epidural Injection, solution Epidural 5 mg/1ml Solution Epidural 50 mg/10ml Injection Epidural 7.5 MG/ML Injection Epidural 5 mg/ml Injection Epidural Injection, solution Epidural Injection, solution Epidural 0625 MG/ML Injection, solution Epidural 1.25 MG/ML - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5708011 No 1998-01-13 2014-10-13 US 
Properties
- State
- Solid
- Experimental Properties
Property Value Source logP 3.6 Not Available pKa 8.1 Not Available - Predicted Properties
Property Value Source Water Solubility 0.0977 mg/mL ALOGPS logP 3.31 ALOGPS logP 4.52 Chemaxon logS -3.5 ALOGPS pKa (Strongest Acidic) 13.62 Chemaxon pKa (Strongest Basic) 8 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 32.34 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 90.19 m3·mol-1 Chemaxon Polarizability 34.43 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - 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 inhibitor Non-inhibitor 0.9099 CYP450 2D6 inhibitor Inhibitor 0.8932 CYP450 2C19 inhibitor Non-inhibitor 0.9026 CYP450 3A4 inhibitor 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
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-006t-6920000000-20e4e8d5c09a52a31c75 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-000i-0290000000-50c6cebcc939057ef7de Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-000e-9840000000-9e401523db8ac590476f Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-000i-0190000000-164b1796be20b943744a Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-01bl-1940000000-ac93156f560d9eba0162 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-9710000000-9fc21a94cd5b33d10194 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-07ix-5980000000-29061bd571f77546d2ab Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 178.4528183 predictedDarkChem Lite v0.1.0 [M-H]- 183.0009183 predictedDarkChem Lite v0.1.0 [M-H]- 173.31892 predictedDeepCCS 1.0 (2019) [M+H]+ 178.8529183 predictedDarkChem Lite v0.1.0 [M+H]+ 183.2863183 predictedDarkChem Lite v0.1.0 [M+H]+ 175.67694 predictedDeepCCS 1.0 (2019) [M+Na]+ 178.4998183 predictedDarkChem Lite v0.1.0 [M+Na]+ 181.77008 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Voltage-gated sodium channel activity
- Specific Function
- Tetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference acro...
- Gene Name
- SCN10A
- Uniprot ID
- Q9Y5Y9
- Uniprot Name
- Sodium channel protein type 10 subunit alpha
- Molecular Weight
- 220623.605 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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. [Article]
- Ueta K, Sugimoto M, Suzuki T, Uchida I, Mashimo T: In vitro antagonism of recombinant ligand-gated ion-channel receptors by stereospecific enantiomers of bupivacaine. Reg Anesth Pain Med. 2006 Jan-Feb;31(1):19-25. [Article]
- Vladimirov M, Nau C, Mok WM, Strichartz G: Potency of bupivacaine stereoisomers tested in vitro and in vivo: biochemical, electrophysiological, and neurobehavioral studies. Anesthesiology. 2000 Sep;93(3):744-55. [Article]
- Brau ME, Branitzki P, Olschewski A, Vogel W, Hempelmann G: Block of neuronal tetrodotoxin-resistant Na+ currents by stereoisomers of piperidine local anesthetics. Anesth Analg. 2000 Dec;91(6):1499-505. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Bajwa SJ, Kaur J: Clinical profile of levobupivacaine in regional anesthesia: A systematic review. J Anaesthesiol Clin Pharmacol. 2013 Oct;29(4):530-9. doi: 10.4103/0970-9185.119172. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- Gurbuzel M, Karaca U, Karayilan N: Genotoxic evaluation of bupivacaine and levobupivacaine in the Drosophila wing spot test. Cytotechnology. 2016 Aug;68(4):979-86. doi: 10.1007/s10616-015-9852-2. Epub 2015 Feb 19. [Article]
- Chalkiadis GA, Anderson BJ, Tay M, Bjorksten A, Kelly JJ: Pharmacokinetics of levobupivacaine after caudal epidural administration in infants less than 3 months of age. Br J Anaesth. 2005 Oct;95(4):524-9. doi: 10.1093/bja/aei218. Epub 2005 Aug 12. [Article]
- Bajwa SJ, Kaur J: Clinical profile of levobupivacaine in regional anesthesia: A systematic review. J Anaesthesiol Clin Pharmacol. 2013 Oct;29(4):530-9. doi: 10.4103/0970-9185.119172. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 02, 2024 22:47