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Identification
NameRopivacaine
Accession NumberDB00296  (APRD00492)
TypeSmall Molecule
GroupsApproved
Description

Ropivacaine is a local anaesthetic drug belonging to the amino amide group. The name ropivacaine refers to both the racemate and the marketed S-enantiomer. Ropivacaine hydrochloride is commonly marketed by AstraZeneca under the trade name Naropin. [Wikipedia]

Structure
Thumb
Synonyms
(S)-(−)-1-propyl-2',6'-pipecoloxylidide
(S)-ropivacaine
L-N-n-propylpipecolic acid-2,6-xylidide
Ropivacaina
Ropivacaine
Ropivacainum
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Naropininjection, solution5 mg/mLepidural; infiltration; perineuralGeneral Injectables & Vaccines, Inc2014-03-11Not applicableUs
Naropininjection, solution10 mg/mLepiduralFresenius Kabi USA, LLC2009-08-04Not applicableUs
Naropininjection, solution7.5 mg/mLepidural; perineuralFresenius Kabi USA, LLC2011-05-31Not applicableUs
Naropininjection, solution5 mg/mLepidural; infiltration; perineuralAPP Pharmaceuticals, LLC2009-08-04Not applicableUs
Naropininjection, solution2 mg/mLepidural; infiltrationFresenius Kabi USA, LLC2009-08-04Not applicableUs
Naropin Inj 10mg/mlsolution10 mgepiduralAstrazeneca Canada Inc1997-04-30Not applicableCanada
Naropin Inj 2mg/mlsolution2 mgblock/infiltration; epiduralAstrazeneca Canada Inc1997-04-30Not applicableCanada
Naropin Inj 5mg/mlsolution5 mgepiduralAstrazeneca Canada Inc1997-04-30Not applicableCanada
Naropin Inj 7.5mg/mlliquid7.5 mgparenteral (unspecified)Astrazeneca Canada Inc1997-04-302003-11-18Canada
Ropivacaine Hydrochloride Injectionsolution2 mgblock/infiltration; epiduralTeva Canada LimitedNot applicableNot applicableCanada
Ropivacaine Hydrochloride Injection USPsolution5 mgblock/infiltration; epiduralHospira Healthcare Corporation2010-12-14Not applicableCanada
Ropivacaine Hydrochloride Injection USPsolution10 mgblock/infiltration; epiduralHospira Healthcare Corporation2010-12-14Not applicableCanada
Ropivacaine Hydrochloride Injection, USPsolution10 mgepiduralFresenius Kabi Canada LtdNot applicableNot applicableCanada
Ropivacaine Hydrochloride Injection, USPsolution7.5 mgnerve block; epiduralFresenius Kabi Canada LtdNot applicableNot applicableCanada
Ropivacaine Hydrochloride Injection, USPsolution5 mgblock/infiltration; epiduralFresenius Kabi Canada LtdNot applicableNot applicableCanada
Ropivacaine Hydrochloride Injection, USPsolution2 mginfiltration; epiduralFresenius Kabi Canada LtdNot applicableNot applicableCanada
Ropivacaine Hydrochloride Injection, USPsolution2 mgblock/infiltrationHospira Healthcare CorporationNot applicableNot applicableCanada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ropivacaine Hydrochlorideinjection, solution7.5 mg/mLepidural; perineuralSagent Pharmaceuticals2014-09-23Not applicableUs
Ropivacaine Hydrochlorideinjection, solution2 mg/mLepidural; infiltrationHospira, Inc.2014-09-23Not applicableUs
Ropivacaine Hydrochlorideinjection, solution10 mg/mLepiduralSagent Pharmaceuticals2014-09-23Not applicableUs
Ropivacaine Hydrochlorideinjection, solution5 mg/mLepidural; infiltration; perineuralSagent Pharmaceuticals2014-09-23Not applicableUs
Ropivacaine Hydrochlorideinjection, solution10 mg/mLparenteralSandoz Inc2014-07-24Not applicableUs
Ropivacaine Hydrochlorideinjection, solution5 mg/mLparenteralSandoz Inc2014-07-24Not applicableUs
Ropivacaine Hydrochlorideinjection, solution10 mg/mLepiduralHospira, Inc.2014-09-23Not applicableUs
Ropivacaine Hydrochlorideinjection, solution5 mg/mLepidural; infiltration; perineuralAkorn, Inc.2016-04-11Not applicableUs
Ropivacaine Hydrochlorideinjection, solution7.5 mg/mLepidural; infiltrationHospira, Inc.2014-09-23Not applicableUs
Ropivacaine Hydrochlorideinjection, solution2 mg/mLepidural; infiltration; perineuralSagent Pharmaceuticals2014-09-23Not applicableUs
Ropivacaine Hydrochlorideinjection, solution5 mg/mLepidural; infiltrationHospira, Inc.2014-09-23Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Ropivacaine hydrochloride
ThumbNot applicableDBSALT000902
Ropivacaine hydrochloride monohydrate
ThumbNot applicableDBSALT001585
Categories
UNII7IO5LYA57N
CAS number84057-95-4
WeightAverage: 274.4011
Monoisotopic: 274.204513464
Chemical FormulaC17H26N2O
InChI KeyInChIKey=ZKMNUMMKYBVTFN-GGYSOQFKNA-N
InChI
InChI=1/C17H26N2O/c1-4-11-19-12-6-5-10-15(19)17(20)18-16-13(2)8-7-9-14(16)3/h7-9,15H,4-6,10-12H2,1-3H3,(H,18,20)/t15-/s2
IUPAC Name
(2S)-N-(2,6-dimethylphenyl)-1-propylpiperidine-2-carboxamide
SMILES
CCCN1CCCC[[email protected]]1C(=O)NC1=C(C)C=CC=C1C
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as alpha amino acid amides. These are amide derivatives of alpha amino acids.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentAlpha amino acid amides
Alternative Parents
Substituents
  • Alpha-amino acid amide
  • N-arylamide
  • Piperidinecarboxylic acid
  • Piperidinecarboxamide
  • 2-piperidinecarboxamide
  • Benzenoid
  • Piperidine
  • Monocyclic benzene moiety
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationUsed in obstetric anesthesia and regional anesthesia for surgery.
PharmacodynamicsRopivacaine, 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 actionLocal anesthetics such as Ropivacaine 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. Specifically, they block the sodium-channel and decrease chances of depolarization and consequent action potentials. In general, the progression of anesthesia is related to the diameter, myelination and conduction velocity of affected nerve fibers.
Related Articles
AbsorptionBioavailability is 87%–98% following epidural administration.
Volume of distributionNot Available
Protein binding94%, mainly to a1-acid glycoprotein
Metabolism

Hepatic

SubstrateEnzymesProduct
Ropivacaine
3-hydroxyropivacaineDetails
Route of eliminationRopivacaine is extensively metabolized in the liver, predominantly by aromatic hydroxylation mediated by cytochrome P4501A to 3-hydroxy ropivacaine. After a single IV dose approximately 37% of the total dose is excreted in the urine as both free and conjugated 3-hydroxy ropivacaine. In total, 86% of the ropivacaine dose is excreted in the urine after intravenous administration of which only 1% relates to unchanged drug.
Half lifeApproximately 4.2 hours.
Clearance
  • 387 +/- 107 mL/min
  • unbound plasma clearance=7.2 +/- 1.6 L/min
ToxicitySystemic exposure to excessive quantities of ropivacaine mainly result in central nervous system (CNS) and cardiovascular effects – CNS effects usually occur at lower blood plasma concentrations and additional cardiovascular effects present at higher concentrations, though cardiovascular collapse may also occur with low concentrations. CNS effects may include CNS excitation (nervousness, tingling around the mouth, tinnitus, tremor, dizziness, blurred vision, seizures) followed by depression (drowsiness, loss of consciousness, respiratory depression and apnea). Cardiovascular effects include hypotension, bradycardia, arrhythmias, and/or cardiac arrest – some of which may be due to hypoxemia secondary to respiratory depression.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Ropivacaine Action PathwayDrug actionSMP00404
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9705
Blood Brain Barrier+0.9377
Caco-2 permeable+0.5912
P-glycoprotein substrateSubstrate0.8037
P-glycoprotein inhibitor IInhibitor0.8768
P-glycoprotein inhibitor IINon-inhibitor0.6339
Renal organic cation transporterNon-inhibitor0.6611
CYP450 2C9 substrateNon-substrate0.819
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateSubstrate0.723
CYP450 1A2 substrateNon-inhibitor0.5499
CYP450 2C9 inhibitorNon-inhibitor0.9246
CYP450 2D6 inhibitorInhibitor0.8821
CYP450 2C19 inhibitorNon-inhibitor0.8773
CYP450 3A4 inhibitorNon-inhibitor0.5902
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6116
Ames testNon AMES toxic0.8507
CarcinogenicityNon-carcinogens0.8763
BiodegradationNot ready biodegradable0.9783
Rat acute toxicity2.2964 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8009
hERG inhibition (predictor II)Inhibitor0.8438
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • App pharmaceuticals llc
Packagers
Dosage forms
FormRouteStrength
Solutionepidural10 mg
Solutionblock/infiltration; epidural2 mg
Solutionepidural5 mg
Liquidparenteral (unspecified)7.5 mg
Injection, solutionepidural10 mg/mL
Injection, solutionepidural; infiltration2 mg/mL
Injection, solutionepidural; infiltration5 mg/mL
Injection, solutionepidural; infiltration7.5 mg/mL
Injection, solutionepidural; infiltration; perineural2 mg/mL
Injection, solutionepidural; infiltration; perineural5 mg/mL
Injection, solutionepidural; perineural7.5 mg/mL
Injection, solutionparenteral10 mg/mL
Injection, solutionparenteral5 mg/mL
Solutionblock/infiltration; epidural10 mg
Solutionblock/infiltration; epidural5 mg
Solutionblock/infiltration2 mg
Solutioninfiltration; epidural2 mg
Solutionnerve block; epidural7.5 mg
Prices
Unit descriptionCostUnit
Ropivacaine hcl-ns 0.5%1.84USD ml
Ropivacaine hcl 0.2% on-q pump0.99USD ml
Naropin 10 mg/ml ampule0.97USD ml
Ropivacaine hcl-ns 0.3%0.9USD ml
Ropivacaine-ns 0.1% on-q pump0.71USD ml
Naropin 7.5 mg/ml ampule0.62USD ml
Naropin 5 mg/ml vial0.58USD ml
Ropivacaine hcl-ns 0.15%0.51USD ml
Ropivacaine hcl-ns 0.125%0.48USD ml
Naropin 5 mg/ml ampule0.46USD ml
Naropin 2 mg/ml ampule0.44USD ml
Ropivacaine hcl-ns 0.1%0.39USD ml
Ropivacaine hcl-ns 0.25%0.34USD ml
Ropivacaine hcl-ns 0.2%0.29USD ml
Naropin 2 mg/ml infusion btl0.23USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA1337549 No1995-11-142012-11-14Canada
CA2165446 No2005-07-052014-05-26Canada
US4870086 No1993-09-242010-09-24Us
US5670524 No1994-05-262014-05-26Us
US7828787 No2005-10-182025-10-18Us
US7857802 No2006-11-282026-11-28Us
US8118802 No2003-05-182023-05-18Us
US8162915 No2004-05-232024-05-23Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubility57.6 mg/LNot Available
logP2.90HANSCH,C ET AL. (1995)
pKa8.07Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.253 mg/mLALOGPS
logP2.91ALOGPS
logP4.07ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)13.62ChemAxon
pKa (Strongest Basic)7.82ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area32.34 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity85.59 m3·mol-1ChemAxon
Polarizability32.67 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Peter Jaksch, “Process for the preparation of ropivacaine hydrochloride monohydrate.” U.S. Patent US5959112, issued February, 1970.

US5959112
General References
  1. Weinberg G, Ripper R, Feinstein DL, Hoffman W: Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity. Reg Anesth Pain Med. 2003 May-Jun;28(3):198-202. [PubMed:12772136 ]
  2. Picard J, Meek T: Lipid emulsion to treat overdose of local anaesthetic: the gift of the glob. Anaesthesia. 2006 Feb;61(2):107-9. [PubMed:16430560 ]
  3. Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, Eisenkraft JB: Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology. 2006 Jul;105(1):217-8. [PubMed:16810015 ]
External Links
ATC CodesN01BB09
AHFS Codes
  • 72:00.00
PDB EntriesNot Available
FDA labelDownload (274 KB)
MSDSDownload (57 KB)
Interactions
Drug Interactions
Drug
AbirateroneThe serum concentration of Ropivacaine can be increased when it is combined with Abiraterone.
BortezomibThe metabolism of Ropivacaine can be decreased when combined with Bortezomib.
CiprofloxacinThe serum concentration of Ropivacaine can be increased when it is combined with Ciprofloxacin.
DeferasiroxThe serum concentration of Ropivacaine can be increased when it is combined with Deferasirox.
FluvoxamineThe serum concentration of Ropivacaine can be increased when it is combined with Fluvoxamine.
HyaluronidaseThe risk or severity of adverse effects can be increased when Hyaluronidase is combined with Ropivacaine.
MexiletineThe metabolism of Ropivacaine can be decreased when combined with Mexiletine.
Peginterferon alfa-2bThe serum concentration of Ropivacaine can be increased when it is combined with Peginterferon alfa-2b.
PropofolThe serum concentration of Ropivacaine can be increased when it is combined with Propofol.
Technetium Tc-99m tilmanoceptRopivacaine may decrease effectiveness of Technetium Tc-99m tilmanocept as a diagnostic agent.
VemurafenibThe serum concentration of Ropivacaine can be increased when it is combined with Vemurafenib.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
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 across the membrane, the protein forms a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient. Plays a role in neuropathic pain mechanisms.
Gene Name:
SCN10A
Uniprot ID:
Q9Y5Y9
Molecular Weight:
220623.605 Da
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:17139284 ]
  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:17016423 ]
  3. Liu BG, Zhuang XL, Li ST, Xu GH: The effects of ropivacaine on sodium currents in dorsal horn neurons of neonatal rats. Anesth Analg. 2000 May;90(5):1034-8. [PubMed:10781449 ]

Enzymes

Kind
Protein
Organism
Human
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 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 N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
References
  1. Arlander E, Ekstrom G, Alm C, Carrillo JA, Bielenstein M, Bottiger Y, Bertilsson L, Gustafsson LL: Metabolism of ropivacaine in humans is mediated by CYP1A2 and to a minor extent by CYP3A4: an interaction study with fluvoxamine and ketoconazole as in vivo inhibitors. Clin Pharmacol Ther. 1998 Nov;64(5):484-91. [PubMed:9834040 ]
  2. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid 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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:
CYP2B6
Uniprot ID:
P20813
Molecular Weight:
56277.81 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
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Drug created on June 13, 2005 07:24 / Updated on May 29, 2016 02:10