Details of the Drug Combination

General Information of Drug Combination (ID: DC1JR7L)

• Drug Combination Name: Gabapentin + Ketorolac
• Indication: Pain; Status: Phase 4 [1]
• Component Drugs:
  Gabapentin (DM6T924): Small molecular drug
  Ketorolac (DMI4EL5): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Gabapentin

Disease Entry	ICD 11	Status	REF
Complex partial seizure	8A68.0	Approved	[2]
Postherpetic neuralgia	1E91.5	Approved	[3]
Solid tumour/cancer	2A00-2F9Z	Phase 3	[2]

Gabapentin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Gamma-aminobutyric acid B receptor (GABBR)	TTDCVZW	GABR1_HUMAN; GABR2_HUMAN	Antagonist	[5]

Gabapentin Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic cation transporter 2 (SLC22A2)	DT9IDPW	S22A2_HUMAN	Substrate	[6]
Organic cation/carnitine transporter 1 (SLC22A4)	DT2EG60	S22A4_HUMAN	Substrate	[7]
L-type amino acid transporter 1 (SLC7A5)	DT48T0N	LAT1_HUMAN	Substrate	[8]

Gabapentin Interacts with 18 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
D(1A) dopamine receptor (DRD1)	OTLZPBT7	DRD1_HUMAN	Increases ADR	[9]
Histamine H1 receptor (HRH1)	OT8F9FV6	HRH1_HUMAN	Increases ADR	[9]
5-hydroxytryptamine receptor 3A (HTR3A)	OTAIV1AK	5HT3A_HUMAN	Increases ADR	[9]
Muscarinic acetylcholine receptor M1 (CHRM1)	OTKW3E6B	ACM1_HUMAN	Increases ADR	[9]
5-hydroxytryptamine receptor 2B (HTR2B)	OTM1AD9J	5HT2B_HUMAN	Increases ADR	[9]
Alpha-1A adrenergic receptor (ADRA1A)	OTUIWCL5	ADA1A_HUMAN	Increases ADR	[9]
5-hydroxytryptamine receptor 2A (HTR2A)	OTWXJX0M	5HT2A_HUMAN	Increases ADR	[9]
Glutamine--fructose-6-phosphate aminotransferase 1 (GFPT1)	OTQBDO45	GFPT1_HUMAN	Increases ADR	[9]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Increases ADR	[9]
Serum paraoxonase/arylesterase 1 (PON1)	OTD0Z2XO	PON1_HUMAN	Decreases Activity	[10]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Activity	[11]
Lactoperoxidase (LPO)	OTJ9QKX9	PERL_HUMAN	Decreases Expression	[12]
Sodium-dependent serotonin transporter (SLC6A4)	OT6FGDLW	SC6A4_HUMAN	Decreases Expression	[12]
Serine/threonine-protein kinase mTOR (MTOR)	OTHH8KU7	MTOR_HUMAN	Decreases Expression	[12]
Glutamate receptor ionotropic, NMDA 1 (GRIN1)	OTZ5YBO8	NMDZ1_HUMAN	Decreases Expression	[12]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[13]
Voltage-dependent calcium channel subunit alpha-2/delta-2 (CACNA2D2)	OTFJXVQQ	CA2D2_HUMAN	Affects Binding	[14]
SH3 and multiple ankyrin repeat domains protein 2 (SHANK2)	OTSQTPFQ	SHAN2_HUMAN	Decreases Expression	[12]

Indication(s) of Ketorolac

Disease Entry	ICD 11	Status	REF
Postoperative inflammation	1A00-CA43.1	Approved	[4]

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	[15]

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	[16]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[16]

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	[17]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Increases Expression	[17]
HLA class I histocompatibility antigen, A alpha chain (HLA-A)	OTAH14LU	HLAA_HUMAN	Affects Expression	[18]
HLA class I histocompatibility antigen, alpha chain E (HLA-E)	OTX1CTFB	HLAE_HUMAN	Affects Expression	[18]
HLA class I histocompatibility antigen, alpha chain G (HLA-G)	OTMLK1KN	HLAG_HUMAN	Affects Expression	[18]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Decreases Expression	[19]
Endothelial PAS domain-containing protein 1 (EPAS1)	OTRE3O8U	EPAS1_HUMAN	Decreases Expression	[19]

References

• [1] ClinicalTrials.gov (NCT02867176) Pain Management in Corneal Collagen Crosslinking for Keratoconus
• [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: 5483).
• [3] Gabapentin FDA Label
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] Gabapentin increases a tonic inhibitory conductance in hippocampal pyramidal neurons. Anesthesiology. 2006 Aug;105(2):325-33.
• [6] Clinical pharmacokinetic drug interaction studies of gabapentin enacarbil, a novel transported prodrug of gabapentin, with naproxen and cimetidine. Br J Clin Pharmacol. 2010 May;69(5):498-507.
• [7] Effects of genetic variation in the novel organic cation transporter, OCTN1, on the renal clearance of gabapentin. Clin Pharmacol Ther. 2008 Mar;83(3):416-21.
• [8] Transport of gabapentin by LAT1 (SLC7A5). Biochem Pharmacol. 2013 Jun 1;85(11):1672-83.
• [9] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [10] Antiepileptic drugs: impacts on human serum paraoxonase-1. J Biochem Mol Toxicol. 2017 Jun;31(6).
• [11] Functional evaluation of polymorphisms in the human ABCB1 gene and the impact on clinical responses of antiepileptic drugs. Pharmacogenet Genomics. 2008 May;18(5):390-402. doi: 10.1097/FPC.0b013e3282f85e36.
• [12] Establishment of a 13 genes-based molecular prediction score model to discriminate the neurotoxic potential of food relevant-chemicals. Toxicol Lett. 2022 Feb 1;355:1-18. doi: 10.1016/j.toxlet.2021.10.013. Epub 2021 Nov 5.
• [13] Effects of the antiepileptic drugs lamotrigine, topiramate and gabapentin on hERG potassium currents. Epilepsy Res. 2005 Jan;63(1):17-25. doi: 10.1016/j.eplepsyres.2004.10.002. Epub 2004 Dec 8.
• [14] Tissue-specific expression and gabapentin-binding properties of calcium channel alpha2delta subunit subtypes. J Membr Biol. 2001 Nov 1;184(1):35-43. doi: 10.1007/s00232-001-0072-7.
• [15] Cyclooxygenase and nitric oxide synthase dependence of cutaneous reactive hyperemia in humans. Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H425-32.
• [16] Body weight, gender and pregnancy affect enantiomer-specific ketorolac pharmacokinetics. Br J Clin Pharmacol. 2017 Sep;83(9):1966-1975.
• [17] 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.
• [18] 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.
• [19] 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.