Details of the Drug Combination

General Information of Drug Combination (ID: DCX6GZ8)

• Drug Combination Name: Levobupivacaine + Ketorolac
• Indication: Total Knee Arthroplasty; Status: Phase 4 [1]
• Component Drugs:
  Levobupivacaine (DM783CH): Small molecular drug
  Ketorolac (DMI4EL5): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Levobupivacaine

Disease Entry	ICD 11	Status	REF
Anaesthesia	9A78.6	Approved	[2]

Levobupivacaine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Sodium channel unspecific (NaC)	TTRK8B9	NOUNIPROTAC	Blocker	[4]

Levobupivacaine Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[5]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[6]

Indication(s) of Ketorolac

Disease Entry	ICD 11	Status	REF
Postoperative inflammation	1A00-CA43.1	Approved	[3]

Ketorolac Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Prostaglandin G/H synthase (COX)	TTK0943	PGH1_HUMAN; PGH2_HUMAN	Inhibitor	[7]

Ketorolac Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[8]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[8]

Ketorolac Interacts with 7 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Prostaglandin G/H synthase 1 (PTGS1)	OTHCRLEC	PGH1_HUMAN	Decreases Expression	[9]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Increases Expression	[9]
HLA class I histocompatibility antigen, A alpha chain (HLA-A)	OTAH14LU	HLAA_HUMAN	Affects Expression	[10]
HLA class I histocompatibility antigen, alpha chain E (HLA-E)	OTX1CTFB	HLAE_HUMAN	Affects Expression	[10]
HLA class I histocompatibility antigen, alpha chain G (HLA-G)	OTMLK1KN	HLAG_HUMAN	Affects Expression	[10]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Decreases Expression	[11]
Endothelial PAS domain-containing protein 1 (EPAS1)	OTRE3O8U	EPAS1_HUMAN	Decreases Expression	[11]

References

• [1] ClinicalTrials.gov (NCT02082067) Total Knee Prosthesis With Continuous Block of Adductor Canal and Outcome
• [2] 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).
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] Block of neuronal tetrodotoxin-resistant Na+ currents by stereoisomers of piperidine local anesthetics. Anesth Analg. 2000 Dec;91(6):1499-505.
• [5] Clinical profile of levobupivacaine in regional anesthesia: A systematic review. J Anaesthesiol Clin Pharmacol. 2013 Oct;29(4):530-9.
• [6] Pharmacokinetics of levobupivacaine after caudal epidural administration in infants less than 3 months of age. Br J Anaesth. 2005 Oct;95(4):524-9.
• [7] Cyclooxygenase and nitric oxide synthase dependence of cutaneous reactive hyperemia in humans. Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H425-32.
• [8] Body weight, gender and pregnancy affect enantiomer-specific ketorolac pharmacokinetics. Br J Clin Pharmacol. 2017 Sep;83(9):1966-1975.
• [9] Acetaminophen selectively suppresses peripheral prostaglandin E2 release and increases COX-2 gene expression in a clinical model of acute inflammation. Pain. 2007 Jun;129(3):279-86.
• [10] Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
• [11] Ibuprofen-mediated reduction of hypoxia-inducible factors HIF-1alpha and HIF-2alpha in prostate cancer cells. Clin Cancer Res. 2003 Aug 1;9(8):3150-7.