Details of the Drug Combination

General Information of Drug Combination (ID: DCEC9GY)

• Drug Combination Name: Potassium Citrate + Torasemide
• Indication: Heart Failure Congenital; Status: Phase 1 [1]
• Component Drugs:
  Potassium Citrate (DMRBUPA): Small molecular drug
  Torasemide (DMXKJ6C): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Potassium Citrate

Disease Entry	ICD 11	Status	REF
Hypokalemia	5C77	Approved	[2]
Kidney stone	GB70.0Z	Approved	[3]
Renal tubular acidosis	N.A.	Approved	[2]

Indication(s) of Torasemide

Disease Entry	ICD 11	Status	REF
Congestive heart failure	BD10	Approved	[4]
Edema	MG29	Approved	[5]
Renal hypoplasia	N.A.	Approved	[6]

Torasemide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Solute carrier family 12 member 1 (SLC12A1)	TTS087L	S12A1_HUMAN	Blocker	[7]

Torasemide Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[8]

Torasemide Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[9]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[10]

Torasemide Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2C9 (CYP2C9)	OTGLBN29	CP2C9_HUMAN	Increases Hydroxylation	[11]
Solute carrier family 12 member 2 (SLC12A2)	OT3ZJ3LH	S12A2_HUMAN	Decreases Activity	[12]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Congenital Mitral Insufficiency	DCCCS4I	N. A.	Phase 1	[13]

References

• [1] ClinicalTrials.gov (NCT06039540) Study of Drug Therapy for Pediatric Heart Failure
• [2] Potassium Citrate FDA Label
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [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: 7312).
• [5] Comparative effects of furosemide and other diuretics in the treatment of heart failure: a systematic review and combined meta-analysis of randomized controlled trials. Heart Fail Rev. 2021 Jan;26(1):127-136.
• [6] Torsemide. 2023 Jul 3. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 JanC.
• [7] Genetic variation in the renal sodium transporters NKCC2, NCC, and ENaC in relation to the effects of loop diuretic drugs. Clin Pharmacol Ther. 2007 Sep;82(3):300-9.
• [8] Coleman J., Cox A. and Cowley N. (2011). Side Effects of Drugs Annual. Elsevier.
• [9] Mechanism-based inactivation of human cytochrome P4502C8 by drugs in vitro. J Pharmacol Exp Ther. 2004 Dec;311(3):996-1007.
• [10] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [11] Allelic and functional variability of cytochrome P4502C9. Pharmacogenetics. 1997 Feb;7(1):51-8. doi: 10.1097/00008571-199702000-00007.
• [12] Azosemide is more potent than bumetanide and various other loop diuretics to inhibit the sodium-potassium-chloride-cotransporter human variants hNKCC1A and hNKCC1B. Sci Rep. 2018 Jun 29;8(1):9877. doi: 10.1038/s41598-018-27995-w.
• [13] ClinicalTrials.gov (NCT06037434) Study of Innovative Drug Treatment Therapy for Pediatric Mitral Regurgitation