Details of the Drug Combination

General Information of Drug Combination (ID: DCDHZFS)

• Drug Combination Name: Ceftriaxone + Octreotide
• Indication: Variceal Hemorrhage; Status: Phase 1 [1]
• Component Drugs:
  Ceftriaxone (DMCEW64): Small molecular drug
  Octreotide (DMHIDCJ): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Ceftriaxone

Disease Entry	ICD 11	Status	REF
Acute gonococcal cervicitis	N.A.	Approved	[2]
Bacteremia	1A73	Approved	[2]
Bacterial arthritis	N.A.	Approved	[2]
Bacterial infection	1A00-1C4Z	Approved	[3]
Chancroid	N.A.	Approved	[2]
Endometritis	N.A.	Approved	[2]
Escherichia coli meningitis	N.A.	Approved	[2]
Gonococcal infection of joint	N.A.	Approved	[2]
Meningococcal meningitis	N.A.	Approved	[2]
Pneumococcal meningitis	N.A.	Approved	[2]
Staphylococcal pneumonia	N.A.	Approved	[2]
Pelvic inflammatory disease	GA05	Investigative	[2]

Ceftriaxone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial Penicillin binding protein (Bact PBP)	TTJP4SM	NOUNIPROTAC	Modulator	[6]

Ceftriaxone Interacts with 4 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[7]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[8]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[9]

Ceftriaxone Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Beta-lactamase (blaB)	DEEAL81	BLA2_KLEPO	Metabolism	[10]
Beta-lactamase (blaB)	DEYIEO5	AMPC_SERMA	Metabolism	[11]
Beta-lactamase (blaB)	DEBKS91	A0A1B1FBM9_ACIBA	Metabolism	[12]

Ceftriaxone Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Dihydrofolate reductase (DHFR)	OT3DVIGM	DYR_HUMAN	Decreases Activity	[13]

Indication(s) of Octreotide

Disease Entry	ICD 11	Status	REF
Acromegaly	5A60.0	Approved	[4]
Carcinoid syndrome	5B10	Approved	[5]
Diabetic retinopathy	9B71.0	Approved	[5]
Neuroendocrine cancer	2B72.1	Investigative	[5]

Octreotide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Somatostatin receptor type 2 (SSTR2)	TTZ6T9E	SSR2_HUMAN	Binder	[15]

Octreotide Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[16]

Octreotide Interacts with 13 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[17]
Glycoprotein hormones alpha chain (CGA)	OT00U3Y3	GLHA_HUMAN	Decreases Secretion	[18]
Thyrotropin subunit beta (TSHB)	OTFDI39D	TSHB_HUMAN	Decreases Secretion	[19]
Prolactin (PRL)	OTWFQGX7	PRL_HUMAN	Affects Expression	[20]
Somatotropin (GH1)	OT92RTRD	SOMA_HUMAN	Decreases Expression	[21]
Insulin (INS)	OTZ85PDU	INS_HUMAN	Decreases Expression	[22]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Decreases Expression	[23]
Insulin-like growth factor I (IGF1)	OTIIZR61	IGF1_HUMAN	Decreases Expression	[24]
Cholecystokinin (CCK)	OT1GCG0L	CCKN_HUMAN	Decreases Secretion	[25]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[26]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[27]
Tumor necrosis factor ligand superfamily member 6 (FASLG)	OTZARCHH	TNFL6_HUMAN	Increases Expression	[26]
Somatostatin (SST)	OTY75GQH	SMS_HUMAN	Decreases Secretion	[27]

References

• [1] ClinicalTrials.gov (NCT03061604) RCT to Determine the Efficacy of Combining Hemospray With Medical Treatment in Acute Variceal Bleeding
• [2] Ceftriaxone FDA Label
• [3] 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: 5326).
• [4] 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: 2055).
• [5] Octreotide FDA Label
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [8] Intestinal transport of beta-lactam antibiotics: analysis of the affinity at the H+/peptide symporter (PEPT1), the uptake into Caco-2 cell monolayers and the transepithelial flux. Pharm Res. 1999 Jan;16(1):55-61.
• [9] Screening of antibiotics that interact with organic anion-transporting polypeptides 1B1 and 1B3 using fluorescent probes. Biol Pharm Bull. 2011;34(3):389-95.
• [10] Antibiotic resistance and production of extended-spectrum beta-lactamases amongst Klebsiella spp. from intensive care units in Europe. J Antimicrob Chemother. 1996 Sep;38(3):409-24.
• [11] Determination of the antibiotic resistance rates of Serratia marcescens isolates obtained from various clinical specimens. Niger J Clin Pract. 2019 Jan;22(1):125-130.
• [12] Drug-resistant genes carried by Acinetobacter baumanii isolated from patients with lower respiratory tract infection. Chin Med J (Engl). 2010 Sep;123(18):2571-5.
• [13] Investigation of the effects of some drugs and phenolic compounds on human dihydrofolate reductase activity. J Biochem Mol Toxicol. 2015 Mar;29(3):135-9.
• [14] [Effects of octreotide on necrosis of hepatocellular carcinoma xenografts in nude mice]. Ai Zheng. 2009 Jul;28(7):673-8. doi: 10.5732/cjc.009.10055.
• [15] Versatile conjugation of octreotide to dendrimers by cycloaddition ("click") chemistry to yield high-affinity multivalent cyclic Peptide dendrimers. Bioconjug Chem. 2009 Jul;20(7):1323-31.
• [16] P-glycoprotein- and mrp2-mediated octreotide transport in renal proximal tubule. Br J Pharmacol. 2000 Jan;129(2):251-6.
• [17] A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
• [18] Treatment of thyroid-stimulating hormone-secreting adenomas with octreotide. Metabolism. 1992 Sep;41(9 Suppl 2):62-5. doi: 10.1016/0026-0495(92)90033-7.
• [19] Long-term efficacy and tolerability of octreotide treatment in acromegaly. Metabolism. 1992 Sep;41(9 Suppl 2):44-50. doi: 10.1016/0026-0495(92)90030-e.
• [20] Long-term treatment of acromegaly with a long-acting analogue of somatostatin, octreotide. Q J Med. 1990 Feb;74(274):189-201.
• [21] Effect of a somatostatin analogue, octreotide, on renal haemodynamics and albuminuria in acromegalic patients. Eur J Clin Invest. 1992 Jul;22(7):494-502. doi: 10.1111/j.1365-2362.1992.tb01496.x.
• [22] Effect of the somatostatin analogue, octreotide, on exercise-induced hypotension in human subjects with chronic sympathetic failure. Clin Sci (Lond). 1995 Oct;89(4):367-73. doi: 10.1042/cs0890367.
• [23] [Inhibitory effect of somatostatin analogue octreotide on the expression of p53 and Ras in human gastric cancer]. Nan Fang Yi Ke Da Xue Xue Bao. 2011 Jun;31(7):1245-8.
• [24] Pharmacokinetics, pharmacodynamics, and safety of microencapsulated octreotide acetate in healthy subjects. J Clin Pharmacol. 2000 May;40(5):475-81. doi: 10.1177/00912700022009242.
• [25] Severe impairment of postprandial cholecystokinin release and gall-bladder emptying and high risk of gallstone formation in acromegalic patients during Sandostatin LAR. Aliment Pharmacol Ther. 2001 Feb;15(2):181-5. doi: 10.1046/j.1365-2036.2001.00924.x.
• [26] [Octreotide induces apoptosis of human hepatoma cells by the mechanism of facilitating the Fas/FasL gene expression therein]. Zhonghua Yi Xue Za Zhi. 2008 Mar 11;88(10):716-8.
• [27] Characterization of the functional and growth properties of long-term cell cultures established from a human somatostatinoma. Endocr Relat Cancer. 2006 Mar;13(1):79-93. doi: 10.1677/erc.1.00988.