LEVOBUPIVACAINE

US Previously Marketed

First approved in 1999

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H28N2O
Molecular Weight	288.4277
Optical Activity	( - )
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=LEBVLXFERQHONN-INIZCTEOSA-N

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

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

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 537		4.4 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 614 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20997lbl.pdf	Primary		Approved 8429	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 1999

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 1737			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP1A2 1054

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20997lbl.pdf#page=4 Page: 4.0	yes
CYP3A4 1737	substrate 3367 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 1647	inhibitor 1626 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
Local anaesthesia in elective inguinal hernia repair: a randomised, double-blind study comparing the efficacy of levobupivacaine with racemic bupivacaine.	2002	12463428
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
Convulsions following axillary brachial plexus blockade with levobupivacaine.	2002 Dec	12437710
The place of ropivacaine in anesthesia.	2003	12872430
Epidural levobupivacaine, ropivacaine and bupivacaine in combination with sufentanil in early labour: a randomized trial.	2003 Aug	12932065
The central nervous system and cardiovascular effects of levobupivacaine and ropivacaine in healthy volunteers.	2003 Aug	12873927
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
Levobupivacaine versus racemic bupivacaine in spinal anaesthesia for urological surgery.	2003 Dec	14719424
A prospective, randomized, double-blind comparison of epidural levobupivacaine 0.5% with epidural ropivacaine 0.75% for lower limb procedures.	2003 Dec	14690101
Efficacy and safety of caudal injection of levobupivacaine, 0.25%, in children under 2 years of age undergoing inguinal hernia repair, circumcision or orchidopexy.	2003 Feb	12562483
[The choice of drugs for caudal anaesthesia in children. An overview].	2003 Jan	12577167
Accidental intravascular injection of levobupivacaine and lidocaine during the transarterial approach to the axillary brachial plexus.	2003 Jan	12514163
Interscalene brachial plexus anesthesia and analgesia for open shoulder surgery: a randomized, double-blinded comparison between levobupivacaine and ropivacaine.	2003 Jan	12505962
Central nervous system and cardiac effects from long-acting amide local anesthetic toxicity in the intact animal model.	2003 Jan-Feb	12567336
The relative toxicity of amitriptyline, bupivacaine, and levobupivacaine administered as rapid infusions in rats.	2003 Jul	12818949
Levobupivacaine versus ropivacaine for sciatic nerve block in the rat.	2003 Jul-Aug	12945022
[Chirocaine in ophthalmology].	2003 Jun	12898725
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
New local anesthetics. Are they worth the cost?	2003 Mar	12698830
Central nervous system toxicity following the administration of levobupivacaine for lumbar plexus block: A report of two cases.	2003 Mar-Apr	12677626
[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
Efficacy, safety, and pharmacokinetics of levobupivacaine with and without fentanyl after continuous epidural infusion in children: a multicenter trial.	2003 Nov	14576555
The relative motor blocking potencies of bupivacaine and levobupivacaine in labor.	2003 Nov	14570676
Perioperative thoracic epidural analgesia in aortic surgery: role of levobupivacaine.	2003 Oct	14673397
Levobupivacaine 0.25% compared with ropivacaine 0.25% by the caudal route in children.	2003 Oct	14580053
Pulmonary uptake of ropivacaine and levobupivacaine in rabbits.	2003 Sep	12933424
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
Density of spinal anaesthetic solutions of bupivacaine, levobupivacaine, and ropivacaine with and without dextrose.	2004 Apr	14766715
Epidural levobupivacaine 0.1% or ropivacaine 0.1% combined with morphine provides comparable analgesia after abdominal surgery.	2004 Feb	14742376
Paravertebral analgesia with levobupivacaine increases postoperative flap tissue oxygen tension after immediate latissimus dorsi breast reconstruction compared with intravenous opioid analgesia.	2004 Feb	14739814
Comparison of patient-controlled epidural bolus administration of 0.1% ropivacaine and 0.1% levobupivacaine, both with 0.0002% fentanyl, for analgesia during labour.	2004 Feb	14725515
Pharmacokinetics of levobupivacaine 0.25% following caudal administration in children under 2 years of age.	2004 Feb	14722171
Changes in transcutaneous carbon dioxide, oxygen saturation, and respiratory rate after interscalene block.	2004 Jan	14746417
A comparison of duration of analgesia of intrathecal 2.5 mg of bupivacaine, ropivacaine, and levobupivacaine in combined spinal epidural analgesia for patients in labor.	2004 Jan	14693626
Levobupivacaine for pediatric spinal anesthesia.	2004 Jan	14693586
Long-term stability of sufentanil citrate with levobupivacaine hydrochloride in 0.9% sodium chloride infusion PVC bags at 4 degrees C.	2004 Jul	15223079
[Levobupivacaine in obstetric analgesia and anaesthesia. Where is its place?].	2004 Jul	15221118
Evidence that intravenous vasopressors can affect rostral spread of spinal anesthesia in pregnancy.	2004 Jul	15220768
Intraoperative and postoperative analgesia with subcutaneous ring block of the penis with levobupivacaine for circumcision in children.	2004 Jun	15211412
Epidural test dose with levobupivacaine and ropivacaine: determination of ED(50) motor block after spinal administration.	2004 Jun	15096445
Postoperative analgesia in infants and children: new developments.	2004 May	15181422
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 15 17:41:55 GMT 2023` Edited by `admin` on `Fri Dec 15 17:41:55 GMT 2023`
Record UNII	A5H73K9U3W
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LEVOBUPIVACAINE

Official Name

English

BUPIVACAINE, (-)-

Common Name

English

BUPIVACAINE (-)-FORM [MI]

Common Name

English

Levobupivacaine [WHO-DD]

Common Name

English

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

Systematic Name

English

BUPIVACAINE (-)-FORM

Common Name

English

LEVOBUPIVACAINE [MART.]

Common Name

English

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

Common Name

English

(-)-BUPIVACAINE

Common Name

English

levobupivacaine [INN]

Common Name

English

BUPIVACAINE, (S)-

Common Name

English

(S)-BUPIVACAINE

Common Name

English

NOVABUPI

Brand Name

English

ROPIVACAINE HYDROCHLORIDE MONOHYDRATE IMPURITY A [EP IMPURITY]

Common Name

English

L-BUPIVACAINE

Common Name

English

LEVOBUPIVACAINE [VANDF]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C245