Details of the Drug

General Information of Drug (ID: DM783CH)

Drug Name

Levobupivacaine

Synonyms

Novabupi; Chirocaine (TN); Levobupivacaine (INN); Levobupivacaine [INN:BAN]; Novabupi (TN); L(-)-Bupivacaine; L-(-)-bupivacaine; L-(-)-1-Butyl-2',6'-pipecoloxylidide; (2S)-1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide; (S)-1-Butyl-2',6'-pipecoloxylidide; (S)-bupivacaine

Indication

Disease Entry	ICD 11	Status	REF
Anaesthesia	9A78.6	Approved	[1]
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Therapeutic Class

Anesthetics

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

288.4

Logarithm of the Partition Coefficient (xlogp)

3.4

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [2]
Clearance: The drug present in the plasma can be removed from the body at the rate of 8.7 mL/min/kg [3]
Elimination: 0.5% of drug is excreted from urine in the unchanged form [2]
Half-life: The concentration or amount of drug in body reduced by one-half in 3.3 hours [3]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 13.00112 micromolar/kg/day [4]
Unbound Fraction: The unbound fraction of drug in plasma is 0.03% [3]
Vd: The volume of distribution (Vd) of drug is 66.91 +/- 18.23 L []
Water Solubility: The ability of drug to dissolve in water is measured as 0.17 mg/mL [2]

Chemical Identifiers

Formula: C18H28N2O
IUPAC Name: (2S)-1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide
Canonical SMILES: CCCCN1CCCC[C@H]1C(=O)NC2=C(C=CC=C2C)C
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
InChIKey: LEBVLXFERQHONN-INIZCTEOSA-N

Cross-matching ID

PubChem CID: 92253
ChEBI ID: CHEBI:6149
CAS Number: 27262-47-1
DrugBank ID: DB01002
TTD ID: D09QUQ
INTEDE ID: DR0934

Combinatorial Drugs (CBD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Sodium channel unspecific (NaC)	TTRK8B9	NOUNIPROTAC	Blocker	[5]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)_{Main DME}	DE4LYSA	CP3A4_HUMAN	Substrate	[6]
Cytochrome P450 1A2 (CYP1A2)_{Main DME}	DEJGDUW	CP1A2_HUMAN	Substrate	[7]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Levobupivacaine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Minor	Increased metabolism of Levobupivacaine caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[8]
Arn-509	DMT81LZ	Minor	Increased metabolism of Levobupivacaine caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[9]
Dronedarone	DMA8FS5	Moderate	Decreased metabolism of Levobupivacaine caused by Dronedarone mediated inhibition of CYP450 enzyme.	Angina pectoris [BA40]	[10]
Nifedipine	DMSVOZT	Moderate	Decreased metabolism of Levobupivacaine caused by Nifedipine mediated inhibition of CYP450 enzyme.	Angina pectoris [BA40]	[11]
Posaconazole	DMUL5EW	Moderate	Decreased metabolism of Levobupivacaine caused by Posaconazole mediated inhibition of CYP450 enzyme.	Aspergillosis [1F20]	[11]
Desipramine	DMT2FDC	Minor	Increased plasma concentration of Levobupivacaine and Desipramine due to competitive binding of plasma proteins.	Attention deficit hyperactivity disorder [6A05]	[12]
Obeticholic acid	DM3Q1SM	Moderate	Decreased metabolism of Levobupivacaine caused by Obeticholic acid mediated inhibition of CYP450 enzyme.	Autoimmune liver disease [DB96]	[11]
Dalfopristin	DM4LTKV	Moderate	Decreased metabolism of Levobupivacaine caused by Dalfopristin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[11]
Clarithromycin	DM4M1SG	Moderate	Decreased metabolism of Levobupivacaine caused by Clarithromycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[11]
Norfloxacin	DMIZ6W2	Moderate	Decreased metabolism of Levobupivacaine caused by Norfloxacin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[11]
Pexidartinib	DMS2J0Z	Minor	Increased metabolism of Levobupivacaine caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[8]
Lapatinib	DM3BH1Y	Moderate	Decreased metabolism of Levobupivacaine caused by Lapatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[11]
Tucatinib	DMBESUA	Moderate	Decreased metabolism of Levobupivacaine caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[11]
Osilodrostat	DMIJC9X	Moderate	Decreased metabolism of Levobupivacaine caused by Osilodrostat mediated inhibition of CYP450 enzyme.	Cushing syndrome [5A70]	[11]
MK-8228	DMOB58Q	Moderate	Decreased metabolism of Levobupivacaine caused by MK-8228 mediated inhibition of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[11]
Nefazodone	DM4ZS8M	Moderate	Decreased metabolism of Levobupivacaine caused by Nefazodone mediated inhibition of CYP450 enzyme.	Depression [6A70-6A7Z]	[11]
Cenobamate	DM8KLU9	Minor	Increased metabolism of Levobupivacaine caused by Cenobamate mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[9]
Stiripentol	DMMSDOY	Moderate	Decreased metabolism of Levobupivacaine caused by Stiripentol mediated inhibition of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[11]
Fosphenytoin	DMOX3LB	Minor	Increased metabolism of Levobupivacaine caused by Fosphenytoin mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[9]
Rufinamide	DMWE60C	Minor	Increased metabolism of Levobupivacaine caused by Rufinamide mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[9]
Phenobarbital	DMXZOCG	Minor	Increased metabolism of Levobupivacaine caused by Phenobarbital mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[11]
Tazemetostat	DMWP1BH	Minor	Increased metabolism of Levobupivacaine caused by Tazemetostat mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[8]
Itraconazole	DMCR1MV	Moderate	Decreased metabolism of Levobupivacaine caused by Itraconazole mediated inhibition of CYP450 enzyme.	Fungal infection [1F29-1F2F]	[11]
Miconazole	DMPMYE8	Moderate	Decreased metabolism of Levobupivacaine caused by Miconazole mediated inhibition of CYP450 enzyme.	Fungal infection [1F29-1F2F]	[11]
Rifampin	DMA8J1G	Minor	Increased metabolism of Levobupivacaine caused by Rifampin mediated induction of CYP450 enzyme.	HIV-infected patients with tuberculosis [1B10-1B14]	[8]
Rifapentine	DMCHV4I	Minor	Increased metabolism of Levobupivacaine caused by Rifapentine mediated induction of CYP450 enzyme.	HIV-infected patients with tuberculosis [1B10-1B14]	[9]
Fosamprenavir	DM4W9B3	Moderate	Decreased metabolism of Levobupivacaine caused by Fosamprenavir mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[11]
Cobicistat	DM6L4H2	Moderate	Decreased metabolism of Levobupivacaine caused by Cobicistat mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[11]
Saquinavir	DMG814N	Moderate	Decreased metabolism of Levobupivacaine caused by Saquinavir mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[11]
Etravirine	DMGV8QU	Minor	Increased metabolism of Levobupivacaine caused by Etravirine mediated induction of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[9]
Darunavir	DMN3GCH	Moderate	Decreased metabolism of Levobupivacaine caused by Darunavir mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[11]
Atazanavir	DMSYRBX	Moderate	Decreased metabolism of Levobupivacaine caused by Atazanavir mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[11]
Teriflunomide	DMQ2FKJ	Minor	Increased metabolism of Levobupivacaine caused by Teriflunomide mediated induction of CYP450 enzyme.	Hyper-lipoproteinaemia [5C80]	[8]
Givosiran	DM5PFIJ	Moderate	Decreased metabolism of Levobupivacaine caused by Givosiran mediated inhibition of CYP450 enzyme.	Inborn porphyrin/heme metabolism error [5C58]	[11]
Amobarbital	DM0GQ8N	Minor	Increased metabolism of Levobupivacaine caused by Amobarbital mediated induction of CYP450 enzyme.	Insomnia [7A00-7A0Z]	[8]
Crizotinib	DM4F29C	Moderate	Decreased metabolism of Levobupivacaine caused by Crizotinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[11]
Ceritinib	DMB920Z	Moderate	Decreased metabolism of Levobupivacaine caused by Ceritinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[11]
PF-06463922	DMKM7EW	Minor	Increased metabolism of Levobupivacaine caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[9]
Osimertinib	DMRJLAT	Minor	Increased metabolism of Levobupivacaine caused by Osimertinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[9]
Capmatinib	DMYCXKL	Moderate	Decreased metabolism of Levobupivacaine caused by Capmatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[11]
Selpercatinib	DMZR15V	Moderate	Decreased metabolism of Levobupivacaine caused by Selpercatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[11]
Primaquine	DMWQ16I	Moderate	Decreased metabolism of Levobupivacaine caused by Primaquine mediated inhibition of CYP450 enzyme.	Malaria [1F40-1F45]	[11]
Idelalisib	DM602WT	Moderate	Decreased metabolism of Levobupivacaine caused by Idelalisib mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[11]
IPI-145	DMWA24P	Moderate	Decreased metabolism of Levobupivacaine caused by IPI-145 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[11]
Vemurafenib	DM62UG5	Minor	Increased metabolism of Levobupivacaine caused by Vemurafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[9]
Dabrafenib	DMX6OE3	Minor	Increased metabolism of Levobupivacaine caused by Dabrafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[9]
Danazol	DML8KTN	Moderate	Decreased metabolism of Levobupivacaine caused by Danazol mediated inhibition of CYP450 enzyme.	Menstrual cycle bleeding disorder [GA20]	[11]
Exjade	DMHPRWG	Moderate	Decreased metabolism of Levobupivacaine caused by Exjade mediated inhibition of CYP450 enzyme.	Mineral absorption/transport disorder [5C64]	[11]
Fedratinib	DM4ZBK6	Moderate	Decreased metabolism of Levobupivacaine caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[11]
Nilotinib	DM7HXWT	Moderate	Decreased metabolism of Levobupivacaine caused by Nilotinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[11]
Dasatinib	DMJV2EK	Moderate	Decreased metabolism of Levobupivacaine caused by Dasatinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[11]
Netupitant	DMEKAYI	Moderate	Decreased metabolism of Levobupivacaine caused by Netupitant mediated inhibition of CYP450 enzyme.	Nausea/vomiting [MD90]	[11]
Rucaparib	DM9PVX8	Moderate	Decreased metabolism of Levobupivacaine caused by Rucaparib mediated inhibition of CYP450 enzyme.	Ovarian cancer [2C73]	[11]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Levobupivacaine caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[13]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Levobupivacaine caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[14]
Lonafarnib	DMGM2Z6	Moderate	Decreased metabolism of Levobupivacaine caused by Lonafarnib mediated inhibition of CYP450 enzyme.	Premature ageing appearance [LD2B]	[11]
Enzalutamide	DMGL19D	Minor	Increased metabolism of Levobupivacaine caused by Enzalutamide mediated induction of CYP450 enzyme.	Prostate cancer [2C82]	[9]
Bicalutamide	DMZMSPF	Moderate	Decreased metabolism of Levobupivacaine caused by Bicalutamide mediated inhibition of CYP450 enzyme.	Prostate cancer [2C82]	[11]
Temsirolimus	DMS104F	Moderate	Increased plasma concentrations of Levobupivacaine and Temsirolimus due to competitive inhibition of the same metabolic pathway.	Renal cell carcinoma [2C90]	[15]
Dexamethasone	DMMWZET	Minor	Increased metabolism of Levobupivacaine caused by Dexamethasone mediated induction of CYP450 enzyme.	Rheumatoid arthritis [FA20]	[9]
Voxelotor	DMCS6M5	Moderate	Decreased metabolism of Levobupivacaine caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[11]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Levobupivacaine caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[11]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Levobupivacaine caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[11]
Armodafinil	DMGB035	Minor	Increased metabolism of Levobupivacaine caused by Armodafinil mediated induction of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[9]
LEE011	DMMX75K	Moderate	Decreased metabolism of Levobupivacaine caused by LEE011 mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[11]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Levobupivacaine caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[16]
Elagolix	DMB2C0E	Minor	Increased metabolism of Levobupivacaine caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[8]
Bretylium	DM1FX74	Moderate	Increased risk of bradycardia by the combination of Levobupivacaine and Bretylium.	Ventricular tachyarrhythmia [BC71]	[17]
Propafenone	DMPIBJK	Moderate	Decreased metabolism of Levobupivacaine caused by Propafenone mediated inhibition of CYP450 enzyme.	Ventricular tachyarrhythmia [BC71]	[11]
Amiodarone	DMUTEX3	Moderate	Increased risk of bradycardia by the combination of Levobupivacaine and Amiodarone.	Ventricular tachyarrhythmia [BC71]	[17]
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References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7211).
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4	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
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6	Clinical profile of levobupivacaine in regional anesthesia: A systematic review. J Anaesthesiol Clin Pharmacol. 2013 Oct;29(4):530-9.
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9	Product Information. Chirocaine (levobupivacaine) Organon, West Orange, NJ.
10	Product Information. Multaq (dronedarone). sanofi-aventis , Bridgewater, NJ.
11	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
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13	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
14	Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
15	Product Information. Prograf (tacrolimus). Fujisawa, Deerfield, IL.
16	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.
17	Keidar S, Grenadier E, Palant A "Sinoatrial arrest due to lidocaine injection in sick sinus syndrome during amiodarone administration." Am Heart J 104 (1982): 1384-5. [PMID: 7148661]