LEVOBUPIVACAINE HYDROCHLORIDE

US Previously Marketed

First approved in 1999

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H28N2O.ClH
Molecular Weight	324.889
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of LEVOBUPIVACAINE HYDROCHLORIDE

Structure Search

SMILES

Cl.CCCCN1CCCC[C@H]1C(=O)NC2=C(C)C=CC=C2C

InChI

InChIKey=SIEYLFHKZGLBNX-NTISSMGPSA-N

InChI=1S/C18H28N2O.ClH/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);1H/t16-;/m0./s1

HIDE SMILES / InChI

Molecular Formula	C18H28N2O
Molecular Weight	288.4277
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20997lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/18728849

Levobupivacaine (CHIROCAINE®) is a (S)-enantiomer of bupivacaine and it is related chemically and pharmacologically to the amino amide class of local anesthetics. Local anesthetics block the generation and the conduction of nerve impulses by increasing the threshold for electrical excitation in the nerve, by slowing 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. Clinically, the order of loss of nerve function is as follows: 1) pain, 2) temperature, 3) touch, 4) proprioception and 5) skeletal muscle tone. Levobupivacaine (CHIROCAINE®) is a safer alternative for regional anesthesia than bupivacaine. It demonstrated less affinity and strength of depressant effects onto myocardial and central nervous vital centers in pharmacodynamic studies, and a superior pharmacokinetic profile.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Sodium channel protein type IV alpha subunit 23 Target ID: CHEMBL3509 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24249993	Blocker 530		4.4 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 607 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20997lbl.pdf	Primary		Approved 8307	CHIROCAINE Approved Use Chirocaine is indicated for the production of local or regional anesthesia for surgery and obstetrics, and for post-operative pain management. Launch Date 9.3381119E11

C_max

Value	Dose	Analyte	Population
0.474 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20997lbl.pdf	1 mg/kg bw single, brachial plexus block dose: 1 mg/kg bw route of administration: Brachial plexus block experiment type: SINGLE co-administered:	LEVOBUPIVACAINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
0.582 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20997lbl.pdf	75 mg single, epidural dose: 75 mg route of administration: Epidural experiment type: SINGLE co-administered:	LEVOBUPIVACAINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
0.811 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20997lbl.pdf	112.5 mg single, epidural dose: 112.5 mg route of administration: Epidural experiment type: SINGLE co-administered:	LEVOBUPIVACAINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
0.961 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20997lbl.pdf	2 mg/kg bw single, brachial plexus block dose: 2 mg/kg bw route of administration: Brachial plexus block experiment type: SINGLE co-administered:	LEVOBUPIVACAINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
2.999 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20997lbl.pdf	1 mg/kg bw single, brachial plexus block dose: 1 mg/kg bw route of administration: Brachial plexus block experiment type: SINGLE co-administered:	LEVOBUPIVACAINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
3.561 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20997lbl.pdf	75 mg single, epidural dose: 75 mg route of administration: Epidural experiment type: SINGLE co-administered:	LEVOBUPIVACAINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
4.93 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20997lbl.pdf	112.5 mg single, epidural dose: 112.5 mg route of administration: Epidural experiment type: SINGLE co-administered:	LEVOBUPIVACAINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
5.311 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20997lbl.pdf	2 mg/kg bw single, brachial plexus block dose: 2 mg/kg bw route of administration: Brachial plexus block experiment type: SINGLE co-administered:	LEVOBUPIVACAINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Analyte	Population
3% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20997lbl.pdf	1 mg/kg bw single, brachial plexus block dose: 1 mg/kg bw route of administration: Brachial plexus block experiment type: SINGLE co-administered:	LEVOBUPIVACAINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
3% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20997lbl.pdf	75 mg single, epidural dose: 75 mg route of administration: Epidural experiment type: SINGLE co-administered:	LEVOBUPIVACAINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
3% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20997lbl.pdf	112.5 mg single, epidural dose: 112.5 mg route of administration: Epidural experiment type: SINGLE co-administered:	LEVOBUPIVACAINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
3% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20997lbl.pdf	2 mg/kg bw single, brachial plexus block dose: 2 mg/kg bw route of administration: Brachial plexus block experiment type: SINGLE co-administered:	LEVOBUPIVACAINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
142.5 mg single, intravenous Dose: 142.5 mg Route: intravenous Route: single Dose: 142.5 mg Sources: https://pubmed.ncbi.nlm.nih.gov/10512284	unhealthy, 77 years n = 1 Health Status: unhealthy Age Group: 77 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/10512284	Sources: https://pubmed.ncbi.nlm.nih.gov/10512284
2 mg/kg single, caudal epidural Dose: 2 mg/kg Route: caudal epidural Route: single Dose: 2 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/16100236	unhealthy, < 3 months n = 22 Health Status: unhealthy Age Group: < 3 months Sex: M+F Population Size: 22 Sources: https://pubmed.ncbi.nlm.nih.gov/16100236	Sources: https://pubmed.ncbi.nlm.nih.gov/16100236
1.75 mg/kg single, subcutaneous Dose: 1.75 mg/kg Route: subcutaneous Route: single Dose: 1.75 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/18761239	unhealthy, >66 years n = 12 Health Status: unhealthy Age Group: >66 years Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/18761239	Sources: https://pubmed.ncbi.nlm.nih.gov/18761239

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1670			inhibitor 1570

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP1A2 1013

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP1A2 1013	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20997lbl.pdf#page=4 Page: 4.0	yes
CYP3A4 1670	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20997lbl.pdf#page=4 Page: 4.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1603	inhibitor 1584 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1573604/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:6149	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:6149
MolPort	MolPort-004-959-713	https://www.molport.com/shop/molecule-link/MolPort-004-959-713
ZINC	ZINC000001530812	http://zinc15.docking.org/substances/ZINC000001530812
eMolecules	36757176	https://www.emolecules.com/cgi-bin/more?vid=36757176

PubMed

Title	Date	PubMed
Levobupivacaine.	2001 Apr	11284819
Cardiac resuscitation after incremental overdosage with lidocaine, bupivacaine, levobupivacaine, and ropivacaine in anesthetized dogs.	2001 Jan	11133597
Does prior administration of enoxaparin influence the effects of levobupivacaine on blood clotting? Assessment using the Thrombelastograph.	2001 Jun	11573588
[Peripheral nerve block. An overview of new developments in an old technique].	2001 May	11417266
Systemic toxicity of levobupivacaine, bupivacaine, and ropivacaine during continuous intravenous infusion to nonpregnant and pregnant ewes.	2001 Nov	11684998
[Levobupivacaine in obstetric analgesia and anaesthesia].	2001 Sep	11778090
A comparison of epidural levobupivacaine 0.5% with or without epinephrine for lumbar spine surgery.	2001 Sep	11524352
Systemic toxicity and resuscitation in bupivacaine-, levobupivacaine-, or ropivacaine-infused rats.	2001 Sep	11524350
Local anaesthesia in elective inguinal hernia repair: a randomised, double-blind study comparing the efficacy of levobupivacaine with racemic bupivacaine.	2002	12463428
Cardiac and CNS toxicity of levobupivacaine: strengths of evidence for advantage over bupivacaine.	2002	11945112
Effects of levobupivacaine, ropivacaine and bupivacaine on HERG channels: stereoselective bupivacaine block.	2002 Dec	12466236
Safety and efficacy of levobupivacaine for postoperative pain relief after the surgical removal of impacted third molars: a comparison with lignocaine and adrenaline.	2002 Dec	12464207
Levobupivacaine versus racemic bupivacaine for spinal anesthesia.	2002 Jan	11772827
Levobupivacaina, bupivacaina racemica e ropivacaina nel blocco del plesso brachiale.	2002 Jul-Aug	12244291
A comparative study of the safety and efficacy of 0.5% levobupivacaine and 0.5% bupivacaine for epidural anesthesia in subjects undergoing elective caesarean section.	2002 Mar	11989042
Clinical properties of levobupivacaine or racemic bupivacaine for sciatic nerve block.	2002 Mar	11943523
Periosteal infusion of bupivacaine/morphine post sternal fracture: a new analgesic technique.	2002 May-Jun	12016608
The place of ropivacaine in anesthesia.	2003	12872430
A comparison of three different concentrations of levobupivacaine for caudal block in children.	2003 Aug	12873919
Comparison of different concentrations of levobupivacaine for post-operative epidural analgesia.	2003 Aug	12859311
A prospective, randomized, double-blind comparison of epidural levobupivacaine 0.5% with epidural ropivacaine 0.75% for lower limb procedures.	2003 Dec	14690101
Preincisional local infiltration of levobupivacaine vs ropivacaine for pain control after laparoscopic cholecystectomy.	2003 Dec	14577025
The relative toxicity of amitriptyline, bupivacaine, and levobupivacaine administered as rapid infusions in rats.	2003 Jul	12818949
Convulsions following axillary brachial plexus blockade with levobupivacaine.	2003 Jun	12846645
Convulsions following axillary brachial plexus blockade with levobupivacaine.	2003 Jun	12846644
Intraoperative epidural anesthesia and postoperative analgesia with levobupivacaine for major orthopedic surgery: a double-blind, randomized comparison of racemic bupivacaine and ropivacaine.	2003 Mar	12719052
Urinary bladder scanning after day-case arthroscopy under spinal anaesthesia: comparison between lidocaine, ropivacaine, and levobupivacaine.	2003 Mar	12594142
[Prevention of cardiovascular accidents during locoregional anesthesia].	2003 May	12768178
Stability of sufentanil and levobupivacaine solutions and a mixture in a 0.9% sodium chloride infusion stored in polypropylene syringes.	2003 May	12729859
Comparison of the effects of intrathecal ropivacaine, levobupivacaine, and bupivacaine for Caesarean section.	2003 Nov	14570791
Onset time, quality of blockade, and duration of three-in-one blocks with levobupivacaine and bupivacaine.	2003 Sep	12933423
Severe phantom leg pain in an amputee after lumbar plexus block.	2003 Sep-Oct	14556141
A comparison of levobupivacaine 0.5% and racemic bupivacaine 0.5% for extradural anesthesia for caesarean section.	2003 Sep-Oct	14556128
Can ropivacaine and levobupivacaine be used as test doses during regional anesthesia?	2004 Apr	15087628
Pharmacokinetics of levobupivacaine 0.25% following caudal administration in children under 2 years of age.	2004 Feb	14722171
Levobupivacaine for pediatric spinal anesthesia.	2004 Jan	14693586
Epidural test dose with levobupivacaine and ropivacaine: determination of ED(50) motor block after spinal administration.	2004 Jun	15096445
High-dose bupivacaine, levobupivacaine and ropivacaine in axillary brachial plexus block.	2004 May	15101856

Patents

Sample Use Guides

In Vivo Use Guide

Surgical anaesthesia: epidural for surgery 10-20 mL (50-150 mg), epidural for cesarean section 20-30 mL (100-150 mg), peripheral nerve 30 mL or 0.4 mL/kg (75-150 mg or 1-2 mg/kg), ophthalmic 5-15 mL (37.5-112.5 mg), local infiltration 60 mL (150 mg). Pain management: epidural for labor analgesia 10-20 mL (25-50 mg), epidural for post-operative pain 4-10 mL/h (5-25 mg/h).

Route of Administration: Intravenous

In Vitro Use Guide

The antagonist activity of levobupivacaine was tested at the human nicotinic acetylcholine (nACh), murine N-methyl-d-aspartate (NMDA), murine gamma-aminobutyric acid(A) (GABA(A)), and human 5-hydroxytryptamine(3A) (5-HT(3A)) receptors expressed in Xenopus oocytes using a 2-voltage clamp technique. The IC50 of levobupivacaine were 950 uM, 65 uM and 85 uM for NMDA, 5-HT(3A), and nACh receptors, respectively. Inhibition of the GABA(A) receptor required concentrations in excess of 10 mM.

Substance Class	Chemical Created by `admin` on `Fri Dec 16 18:32:12 UTC 2022` Edited by `admin` on `Fri Dec 16 18:32:12 UTC 2022`
Record UNII	J998RDZ51I
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LEVOBUPIVACAINE HYDROCHLORIDE

Official Name

English

BUPIVACAINE (-)-FORM HYDROCHLORIDE [MI]

Common Name

English

(S)-1-BUTYL-N-(2,6-DIMETHYLPHENYL)-2-PIPERIDINECARBOXAMIDE MONOHYDROCHLORIDE

Systematic Name

English

LEVOBUPIVACAINE HYDROCHLORIDE [JAN]

Common Name

English

LEVOBUPIVACAINE HCL [VANDF]

Common Name

English

LEVOBUPIVACAINE HYDROCHLORIDE [MART.]

Common Name

English

LEVOBUPIVACAINE HYDROCHLORIDE [USAN]

Common Name

English

(S)-1-BUTYL-2',6'-PIPECOLOXYLIDIDE MONOHYDROCHLORIDE

Common Name

English

Levobupivacaine hydrochloride [WHO-DD]

Common Name

English

LEVOBUPIVACAINE HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

CHIROCAINE

Code

English

LEVOBUPIVACAINE HCL

Common Name

English

BUPIVACAINE (-)-FORM HYDROCHLORIDE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C245