Details of the Drug

General Information of Drug (ID: DMHPD2Y)

• Drug Name: SODIUM CITRATE
• Synonyms: Sodium citrate; 68-04-2; TRISODIUM CITRATE; Citrosodine; Sodium citrate anhydrous; Citrosodina; Natrocitral; Citrosodna; Citreme; Citnatin; sodium citrate, anhydrous; Sodium 2-hydroxypropane-1,2,3-tricarboxylate; Trisodium citrate anhydrous; Citric acid, trisodium salt; Trisodium citrate, anhydrous; Citric acid trisodium salt; 1,2,3-Propanetricarboxylic acid, 2-hydroxy-, trisodium salt; UNII-RS7A450LGA; FEMA No. 3026; CCRIS 3293; Sodium citrate (Na3C6H5O7); HSDB 5201; EINECS 200-675-3; RS7A450LGA; CHEBI:53258; Trisodium 2-hydroxy-1

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight; 258.07
  Topological Polar Surface Area; Not Available
  Rotatable Bond Count; 2
  Hydrogen Bond Donor Count; 1
  Hydrogen Bond Acceptor Count; 7
• ADMET Property:
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 1.6-2.1 h [2]
  Clearance: The total body clearance of drug is 313-1107 mL/min [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 18 - 54 minutes [2]
  Metabolism: The drug is metabolized via the liver [3]
  Vd: The volume of distribution (Vd) of drug is 19-39 L [2]
• Chemical Identifiers:
  Formula: C6H5Na3O7
  IUPAC Name: trisodium;2-hydroxypropane-1,2,3-tricarboxylate
  Canonical SMILES: C(C(=O)[O-])C(CC(=O)[O-])(C(=O)[O-])O.[Na+].[Na+].[Na+]
  InChI: InChI=1S/C6H8O7.3Na/c7-3(8)1-6(13,5(11)12)2-4(9)10;;;/h13H,1-2H2,(H,7,8)(H,9,10)(H,11,12);;;/q;3*+1/p-3
  InChIKey: HRXKRNGNAMMEHJ-UHFFFAOYSA-K
• Cross-matching ID:
  PubChem CID: 6224
  ChEBI ID: CHEBI:53258
  CAS Number: 68-04-2
  DrugBank ID: DB09154
  TTD ID: D05KTE

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Carbonic anhydrase IV (CA-IV)	TTZHA0O	CAH4_HUMAN	Inhibitor	[1]

Molecular Expression Atlas of This Drug

• The Studied Disease: Discovery agent
• ICD Disease Classification: N.A.

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Carbonic anhydrase IV (CA-IV)	DTT	CA4	1.58E-77	-2.02	-1.77

Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Pexidartinib	DMS2J0Z	Moderate	Decreased absorption of SODIUM CITRATE due to altered gastric pH caused by Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[11]
HKI-272	DM6QOVN	Moderate	Decreased absorption of SODIUM CITRATE due to altered gastric pH caused by HKI-272.	Breast cancer [2C60-2C6Y]	[12]
GSK1265744	DMT8J0I	Moderate	Decreased absorption of SODIUM CITRATE due to altered gastric pH caused by GSK1265744.	Human immunodeficiency virus disease [1C60-1C62]	[13]
Acalabrutinib	DM7GCVW	Moderate	Decreased absorption of SODIUM CITRATE due to altered gastric pH caused by Acalabrutinib.	Mature B-cell lymphoma [2A85]	[14]
Choline salicylate	DM8P137	Moderate	as urine pH determines the ionization state of weakly acidic or weakly alkaline drugs. SODIUM CITRATE caused by Choline salicylate mediated altered urine pH.	Postoperative inflammation [1A00-CA43]	[15]

References

• [1] Carbonic anhydrase inhibitors. Interaction of isozymes I, II, IV, V, and IX with carboxylates. Bioorg Med Chem Lett. 2005 Feb 1;15(3):573-8.
• [2] Citrate pharmacokinetics and metabolism in cirrhotic and noncirrhotic critically ill patients. Crit Care Med. 2003 Oct;31(10):2450-5.
• [3] Claessens AJ, Risler LJ, Eyal S, Shen DD, Easterling TR, Hebert MF: CYP2D6 mediates 4-hydroxylation of clonidine in vitro: implication for pregnancy-induced changes in clonidine clearance. Drug Metab Dispos. 2010 Sep;38(9):1393-6. doi: 10.1124/dmd.110.033878. Epub 2010 Jun 22.
• [4] Carbonic anhydrase inhibitors: inhibition of mammalian isoforms I-XIV with a series of substituted phenols including paracetamol and salicylic acid. Bioorg Med Chem. 2008 Aug 1;16(15):7424-8.
• [5] Carbonic anhydrase inhibitors. Inhibition of the membrane-bound human and bovine isozymes IV with sulfonamides. Bioorg Med Chem Lett. 2005 Feb 15;15(4):1149-54.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] Carbonic anhydrase inhibitors. Antioxidant polyphenols effectively inhibit mammalian isoforms I-XV. Bioorg Med Chem Lett. 2010 Sep 1;20(17):5050-3.
• [8] Carbonic anhydrase inhibitors. Inhibition of mammalian isoforms I-XIV with a series of natural product polyphenols and phenolic acids. Bioorg Med Chem. 2010 Mar 15;18(6):2159-2164.
• [9] Carbonic anhydrase inhibitors. Interaction of the antitumor sulfamate EMD 486019 with twelve mammalian carbonic anhydrase isoforms: Kinetic and X-r... Bioorg Med Chem Lett. 2008 Aug 1;18(15):4282-6.
• [10] Carbonic anhydrase inhibitors: crystallographic and solution binding studies for the interaction of a boron-containing aromatic sulfamide with mamm... Bioorg Med Chem Lett. 2010 Jun 15;20(12):3601-5.
• [11] Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
• [12] Product Information. Nerlynx (neratinib). Puma Biotechnology, Inc., Los Angeles, CA.
• [13] Cerner Multum, Inc. "Canadian Product Information.".
• [14] Product Information. Calquence (acalabrutinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
• [15] Balali-Mood M, Prescott LF "Failure of alkaline diuresis to enhance diflunisal elimination." Br J Clin Pharmacol 10 (1980): 163-5. [PMID: 7426277]