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Identification
Name Levobupivacaine
Accession Number DB01002 (APRD00110)
Type small molecule
Groups approved
Description

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. Compared to bupivacaine, levobupivacaine is associated with less vasodilation and has a longer duration of action. 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. Adverse drug reactions (ADRs) are rare when it is administered correctly. Most ADRs relate to administration technique (resulting in systemic exposure) or pharmacological effects of anesthesia, however allergic reactions can rarely occur. [Wikipedia]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Levobupivacaine hydrochloride
Salts Not Available
Brand names
Name Company
Chirocaine Abbott Laboratories
Brand mixtures Not Available
Categories
  • Anesthetics
  • Anesthetics, Local
CAS number 27262-47-1
Weight Average: 288.4277
Monoisotopic: 288.220163528
Chemical Formula C18H28N2O
InChI Key InChIKey=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
Plain Text
IUPAC Name
(2S)-1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide
SMILES
CCCCN1CCCC[C@H]1C(=O)NC1=C(C)C=CC=C1C
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Acetanilides
Substructures
  • Amino Ketones
  • Benzene and Derivatives
  • Acetanilides
  • Carboxylic Acids and Derivatives
  • Aliphatic and Aryl Amines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Anilines
  • Piperidines
Pharmacology
Indication For the production of local or regional anesthesia for surgery and obstetrics, and for post-operative pain management
Pharmacodynamics 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.
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]
Toxicity 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.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00397 Levobupivacaine Pathway SMP00397
Pharmacoeconomics
Manufacturers
  • Purdue pharma lp
Packagers
Dosage forms
Form Route Strength
Solution Parenteral
Prices Not Available
Patents
Country Patent Number Approved Expires (estimated)
United States 5708011 1994-10-13 2014-10-13
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 9.77e-02 g/l 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 ChemAxon
rotatable bond count 5 ChemAxon
refractivity 90.19 ChemAxon
polarizability 34.45 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. 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. Pubmed 18788503
  2. http://www.orgyn.com/resources/genrx/D003445.asp
  3. Burlacu CL, Buggy DJ: Update on local anesthetics: focus on levobupivacaine. Ther Clin Risk Manag. 2008 Apr;4(2):381-92. Pubmed
External Links
Resource Link
KEGG Compound C07887 Link_out
PubChem Compound 92253 Link_out
PubChem Substance 46505295 Link_out
ChemSpider 83289 Link_out
ChEBI 6149 Link_out
ChEMBL 6149 Link_out
Therapeutic Targets Database DAP001233 Link_out
PharmGKB PA164754741 Link_out
RxList http://www.rxlist.com/cgi/generic2/levobupivacaine.htm Link_out
Wikipedia http://en.wikipedia.org/wiki/Levobupivacaine Link_out
ATC Codes
  • N01BB10
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (2.72 MB)
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Sodium channel protein type 10 subunit alpha

Pharmacological action: yes
Actions: inhibitor

This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant sodium channel isoform. Its electrophysiological properties vary depending on the type of the associated beta subunits (in vitro). Plays a role in neuropathic pain mechanisms

Organism class: human
UniProt ID: Q9Y5Y9 Link_out
Gene: SCN10A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. 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. Pubmed
  4. 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. Pubmed
  5. 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. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

2. Cytochrome P450 1A2

Actions: substrate

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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 February 08, 2013 16:19