Identification

Name
Sodium Citrate
Accession Number
DB09154  (DB09159)
Type
Small Molecule
Groups
Approved, Investigational
Description

Sodium citrate is the sodium salt of citric acid. It is white, crystalline powder or white, granular crystals, slightly deliquescent in moist air, freely soluble in water, practically insoluble in alcohol. Like citric acid, it has a sour taste. From the medical point of view, it is used as alkalinizing agent. It works by neutralizing excess acid in the blood and urine. It has been indicated for the treatment of metabolic acidosis.

Structure
Thumb
Synonyms
  • Anhydrous sodium citrate
  • Anhydrous trisodium citrate
  • Citric acid, trisodium salt
  • Natrii citras
  • Natrocitral
  • Sodium citrate anhydrous
  • Sodium citrate, anhydrous
  • Sodium citrate,anhydrous
  • trisodium citrate anhydrous
  • Trisodium citrate, anhydrous
  • Trisodium-citrate
External IDs
E-331(III) / FEMA NO. 3026, ANHYDROUS- / INS NO.331(III) / INS-331(III)
Product Ingredients
IngredientUNIICASInChI Key
Sodium citrate dihydrateB22547B95K6132-04-3NLJMYIDDQXHKNR-UHFFFAOYSA-K
Active Moieties
NameKindUNIICASInChI Key
Citric AcidunknownXF417D3PSL77-92-9KRKNYBCHXYNGOX-UHFFFAOYSA-N
Sodium cationionicLYR4M0NH3717341-25-2FKNQFGJONOIPTF-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Anticoagulant Sod Citrate Soltn 4gm/100mlSolution4 gUnknownBaxter Laboratories1990-12-31Not applicableCanada
Anticoagulant Sodium CitrateSolution10 g/250mLIntravenousMedsep Corporation2011-04-15Not applicableUs
Anticoagulant Sodium Citrate 4% W/V Solution, USPSolution4 gUnknownHaemonetics Corporation2012-10-01Not applicableCanada
Anticoagulant Sodium Citrate Sol 4% USPLiquid4 %IntravenousCutter Med & Biol, Division Of Miles Canada Ltd.1988-12-311996-09-09Canada
Anticoagulant Sodium Citrate Solution USPSolution4 gUnknownFenwal, Inc.2011-11-01Not applicableCanada
Haemonetics Anticoagulant Sodium CitrateSolution40 mg/1mLExtracorporealHaemonetics Corporation2013-01-10Not applicableUs
Sodium CitrateSolution10.0 g/250mLIntravenousHaemonetics Corporation1978-06-30Not applicableUs
Sodium Citrate Blood-Pack Units, (PL 146 Plastic)Solution4 g/100mLIntravenousFresenius Kabi2014-09-29Not applicableUs
Sodium Citrate Blood-Pack Units, (PL 146 Plastic)Solution2 g/50mLIntravenousFenwal, Inc.2007-03-01Not applicableUs
Sodium Citrate Blood-Pack Units, (PL 146 Plastic)Solution4 g/100mLIntravenousFenwal, Inc.2007-03-01Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Sodium Citrate 4% w/v AnticoagulantInjection, solution4 g/100mLIntravenousTerumo Bct, Ltd2018-06-26Not applicableUs
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Bromo SeltzerPowder3.5 gOralWarner Lambert Canada Inc.1976-12-311999-08-13Canada
Lemon Eno 2650mg/pckPowder2.65 gOralSmithkline Beecham Consumer Healthcare, Division Of Smithkline Beecham Inc.1994-12-311998-08-25Canada
Orange Eno 2645mg/pckPowder2.645 gOralSmithkline Beecham Consumer Healthcare, Division Of Smithkline Beecham Inc.1994-12-311998-08-25Canada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
A-C-D SolutionSodium Citrate (250 mg) + Citric Acid (80 mg) + Dextrose, unspecified form (132 mg)LiquidIntravenousDraximage A Division Of Draxis Specialty Pharmaceuticals Inc1959-12-312003-07-08Canada
Acd ASodium citrate dihydrate (2.2 g/100mL) + Citric acid monohydrate (0.8 g/100mL) + D-glucose monohydrate (2.45 g/100mL)Injection, solutionIntravenousTerumo Bct, Ltd.2002-02-25Not applicableUs
Acd ASodium Citrate (2.2 g/100mL) + Citric acid monohydrate (0.80 g/100mL) + D-glucose monohydrate (2.45 g/100mL)Injection, solutionIntravenousTerumo Bct2002-02-25Not applicableUs
Acd ASodium citrate dihydrate (2.2 g/100mL) + Citric acid monohydrate (0.8 g/100mL) + D-glucose monohydrate (2.45 g/100mL)Injection, solutionIntravenousTerumo Bct, Ltd.2002-02-25Not applicableUs
ACD Blood-Pack Units (PL 146 Plastic)Sodium citrate dihydrate (1.48 g/67.5mL) + Citric Acid (493 mg/67.5mL) + D-glucose monohydrate (1.65 g/67.5mL)SolutionIntravenousFenwal, Inc.2007-03-01Not applicableUs
Acd-ASodium Citrate (2.20 g/100mL) + Citric acid monohydrate (0.73 g/100mL) + D-glucose monohydrate (2.45 g/100mL)SolutionIntravenousHaemonetics Corporation1987-11-06Not applicableUs
Acd-ASodium Citrate (2.2 g/100mL) + Citric Acid (730 mg/100mL) + D-glucose monohydrate (2.45 g/100mL)SolutionIntravenousFenwal, Inc.2012-10-24Not applicableUs
Acd-ASodium Citrate (11 g/500mL) + Citric Acid (3.65 g/500mL) + D-glucose monohydrate (12.25 g/500mL)SolutionIntravenousFenwal, Inc.2007-03-01Not applicableUs
Additive Solution Formula 3 As-3Sodium citrate dihydrate (0.588 g) + Adenine (0.030 g) + Citric acid monohydrate (0.042 g) + Dextrose, unspecified form (1.10 g) + Sodium Chloride (0.410 g) + Sodium phosphate, monobasic, monohydrate (0.276 g)SolutionUnknownTerumo Bct, Inc.2013-05-31Not applicableCanada
ADSOL Red Cell Preservation Solution System in Plastic Container (PL 146 Plastic)Sodium citrate dihydrate (1.84 g/70mL) + Adenine (30 mg/110mL) + Citric Acid (209 mg/70mL) + D-glucose monohydrate (1.78 g/70mL) + D-glucose monohydrate (2.42 g/110mL) + Mannitol (825 mg/110mL) + Sodium Chloride (990 mg/110mL) + Sodium phosphate, monobasic, monohydrate (155 mg/70mL)KitFenwal, Inc.2007-03-01Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Anticoagulant Citrate Dextrose Solution-ASodium Citrate (2.20 g/100mL) + Citric acid monohydrate (0.73 g/100mL) + Dextrose, unspecified form (2.45 g/100mL)SolutionExtracorporealBiomet Biologics2010-01-012010-09-06Us
Cytosol Ophthalmics - Balanced Salt SolutionSodium citrate dihydrate (1.70 mg/1mL) + Calcium chloride dihydrate (48 mg/1mL) + Magnesium chloride hexahydrate (30 mg/1mL) + Potassium Chloride (75 mg/1mL) + Sodium Chloride (6.40 mg/1mL) + Sodium acetate trihydrate (3.90 mg/1mL)SolutionIrrigationBiomet Biologics2010-01-012010-09-04Us
Cytra 3Sodium Citrate (500 mg/5mL) + Citric acid monohydrate (334 mg/5mL) + Potassium Citrate (550 mg/5mL)SyrupOralPegasus Laboratories2006-05-052009-10-17Us
Cytra 3Sodium Citrate (500 mg/5mL) + Citric acid monohydrate (334 mg/5mL) + Potassium Citrate (550 mg/5mL)SyrupOralCypress Pharmaceuticals, Inc2008-07-292014-10-11Us
Cytra-2Sodium citrate dihydrate (500 mg/5mL) + Citric acid monohydrate (334 mg/5mL)LiquidOralPegasus Laboratories2006-05-052010-12-30Us
Cytra-2Sodium citrate dihydrate (500 mg/5mL) + Citric acid monohydrate (334 mg/5mL)SolutionOralCypress Pharmaceuticals, Inc.2008-10-012014-10-11Us
EnLyteSodium Citrate (3.67 mg/1) + 1,2-docosahexanoyl-sn-glycero-3-phosphoserine calcium (6.4 mg/1) + 1,2-icosapentoyl-sn-glycero-3-phosphoserine calcium (800 ug/1) + Citric acid monohydrate (1.83 mg/1) + Cobamamide (50 ug/1) + Cocarboxylase (25 ug/1) + Ferrous cysteine glycinate (13.6 mg/1) + Flavin adenine dinucleotide (25 ug/1) + Folic Acid (1 mg/1) + Glycine betaine (500 ug/1) + Leucovorin (2.5 mg/1) + Levomefolate magnesium (7 mg/1) + Magnesium ascorbate (24 mg/1) + NADH (25 ug/1) + Phosphatidyl serine (12 mg/1) + Pyridoxal Phosphate (25 ug/1) + Magnesium L-threonate (1 mg/1) + Zinc ascorbate (1 mg/1)Capsule, delayed release pelletsOralJaymac Pharmaceuticals Llc2011-10-01Not applicableUs
NauzeneSodium citrate dihydrate (230 mg/1)Tablet, chewableOralAlva Amco Pharmacal Companies, Inc.2000-07-08Not applicableUs
Nauzene GrapeSodium citrate dihydrate (0.921 g/15mL)SyrupOralAlva-Amco Pharmacal Companies, Inc.2012-04-242014-01-03Us
OracitSodium citrate dihydrate (490 mg/5mL) + Citric acid monohydrate (640 mg/5mL)SolutionOralCmp Pharma, Inc.1984-05-15Not applicableUs
Categories
UNII
RS7A450LGA
CAS number
68-04-2
Weight
Average: 258.068
Monoisotopic: 257.97283534
Chemical Formula
C6H5Na3O7
InChI Key
HRXKRNGNAMMEHJ-UHFFFAOYSA-K
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
IUPAC Name
trisodium 2-hydroxypropane-1,2,3-tricarboxylate
SMILES
[Na+].[Na+].[Na+].OC(CC([O-])=O)(CC([O-])=O)C([O-])=O

Pharmacology

Indication

Used as an anticoagulant during plasmophoresis as well as a neutralizing agent in the treatment of upset stomach and acidic urine [Label] [6] [7].

Associated Conditions
Associated Therapies
Pharmacodynamics

Citrate prevents activation of the clotting cascade by chelating calcium ions. Citrate neutralizes acid in the stomach and urine, raising the pH [8].

Mechanism of action

Citrate chelates free calcium ions preventing them from forming a complex with tissue factor and coagulation factor VIIa to promote the activation of coagulation factor X [1] [2]. This inhibits the extrinsic initiation of the coagulation cascade. Citrate may also exert an anticoagulant effect via a so far unknown mechanism as restoration of calcium concentration does not fully reverse the effect of citrate [1]. Citrate is a weak base and so reacts with hydrochloric acid in the stomach to raise the pH. It it further metabolized to bicarbonate which then acts as a systemic alkalizing agent, raising the pH of the blood and urine [8]. It also acts as a diuretic and increases the urinary excretion of calcium.

Absorption

Tmax of 98-130min [3].

Volume of distribution

19-39L [3].

Protein binding
Not Available
Metabolism

Citrate is metabolized to bicarbonate in the liver and plays a role as an intermediate in the citric acid cycle [5] [9].

Route of elimination

Largely eliminated through hepatic metabolism with very little cleared by the kidneys [3] [4].

Half life

18-54 min [3]

Clearance

Total clearance of 313-1107mL/min [3].

Toxicity

Overdose toxicity is mainly due to alkalosis as well as tetany or depressed heart function due to lack of free calcium [8].

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinSodium Citrate may increase the anticoagulant activities of (R)-warfarin.
(S)-WarfarinSodium Citrate may increase the anticoagulant activities of (S)-Warfarin.
4-hydroxycoumarinSodium Citrate may increase the anticoagulant activities of 4-hydroxycoumarin.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Sodium Citrate.
AceclofenacThe risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with Sodium Citrate.
AcenocoumarolAcenocoumarol may increase the anticoagulant activities of Sodium Citrate.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Sodium Citrate.
AlaproclateAlaproclate may increase the antiplatelet activities of Sodium Citrate.
AlclofenacThe risk or severity of bleeding and hemorrhage can be increased when Alclofenac is combined with Sodium Citrate.
AllylestrenolAllylestrenol may decrease the anticoagulant activities of Sodium Citrate.
Food Interactions
Not Available

References

General References
  1. Mann KG, Whelihan MF, Butenas S, Orfeo T: Citrate anticoagulation and the dynamics of thrombin generation. J Thromb Haemost. 2007 Oct;5(10):2055-61. [PubMed:17883701]
  2. Palta S, Saroa R, Palta A: Overview of the coagulation system. Indian J Anaesth. 2014 Sep;58(5):515-23. doi: 10.4103/0019-5049.144643. [PubMed:25535411]
  3. Kramer L, Bauer E, Joukhadar C, Strobl W, Gendo A, Madl C, Gangl A: Citrate pharmacokinetics and metabolism in cirrhotic and noncirrhotic critically ill patients. Crit Care Med. 2003 Oct;31(10):2450-5. [PubMed:14530750]
  4. Zheng Y, Xu Z, Zhu Q, Liu J, Qian J, You H, Gu Y, Hao C, Jiao Z, Ding F: Citrate Pharmacokinetics in Critically Ill Patients with Acute Kidney Injury. PLoS One. 2013 Jun 18;8(6):e65992. doi: 10.1371/journal.pone.0065992. Print 2013. [PubMed:23824037]
  5. Li K, Xu Y: Citrate metabolism in blood transfusions and its relationship due to metabolic alkalosis and respiratory acidosis. Int J Clin Exp Med. 2015 Apr 15;8(4):6578-84. eCollection 2015. [PubMed:26131288]
  6. FDA Monograph: Sodium Citrate Tablet [Link]
  7. FDA Monograph: Sodium Citrate Liquid [Link]
  8. TOXNET: Trisodium Citrate [Link]
  9. SMPDB: Citric Acid Cycle [Link]
External Links
KEGG Drug
D05855
PubChem Compound
6224
PubChem Substance
310265067
ChemSpider
5989
ChEBI
53258
ChEMBL
CHEMBL1355
Wikipedia
Sodium_citrate
ATC Codes
B05CB02 — Sodium citrate
AHFS Codes
  • 56:04.00 — Antacids and Adsorbents
  • 20:12.04.92 — Miscellaneous Anticoagulants
  • 56:92.00 — Miscellaneous GI Drugs
FDA label
Download (124 KB)
MSDS
Download (77.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedTreatmentHeart Defects,Congenital / Respiratory Insufficiency1
1CompletedTreatmentIron-refractory, Iron-deficiency Anemia (IRIDA)1
1WithdrawnTreatmentArthritis1
1, 2CompletedOtherGlaucoma1
2Active Not RecruitingTreatmentCardiopulmonary Bypass / Surgery, Cardiac1
2CompletedTreatmentCataracts1
2CompletedTreatmentIron-Refractory Iron-Deficiency Anemia1
2CompletedTreatmentSymptomatic Focal Vitreomacular Adhesion1
2Not Yet RecruitingTreatmentMethicillin-Resistant Staphylococcus Aureus (MRSA) / Skin-structure infections1
2, 3CompletedTreatmentGlaucoma1
3Unknown StatusTreatmentRejection, Transplant1
4CompletedPreventionInflammatory Reaction1
4CompletedTreatmentPsoriasis / Sleep Apnea, Obstructive1
4WithdrawnTreatmentClostridium Difficile Infection (CDI)1
Not AvailableCompletedScreeningConotruncal Cardiac Defects / Heart Defects,Congenital / Parathyroid deficiency / Pulmonary Atresia / Pulmonary Valve Stenosis / Tetralogy Of Fallot1
Not AvailableCompletedTreatmentCataracts1
Not AvailableRecruitingNot AvailableIntra Operative Bleeding, Blood Salvage1
Not AvailableRecruitingTreatmentShock / Shock, Septic1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
LiquidIntravenous
Injection, solutionIntravenous
Kit
SolutionIntraocular
SolutionIntravenous
Injection, solutionExtracorporeal
SolutionUnknown
SolutionExtracorporeal
SolutionUnknown4 g
SolutionIntravenous10 g/250mL
LiquidIntravenous4 %
SolutionIrrigation
PowderOral3.5 g
SolutionOphthalmic
Granule, effervescentOral
Capsule, delayed release pelletsOral
SolutionExtracorporeal40 mg/1mL
KitIntravenous
LiquidIntraocular
PowderOral2.65 g
LiquidOral
SyrupOral
Enema; liquidRectal
LiquidRectal
Tablet, chewableOral230 mg/1
SyrupOral0.921 g/15mL
PowderOral2.645 g
PowderOral
Tablet, chewableOral
SolutionIntravenous10.0 g/250mL
Injection, solutionIntravenous4 g/100mL
SolutionIntravenous2 g/50mL
SolutionIntravenous4 g/100mL
SolutionExtracorporeal14 g/30mL
SolutionOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)300MSDS
water solubility29.4g/LMSDS
Predicted Properties
PropertyValueSource
Water Solubility73.7 mg/mLALOGPS
logP-0.55ALOGPS
logP-1.3ChemAxon
logS-0.54ALOGPS
pKa (Strongest Acidic)3.05ChemAxon
pKa (Strongest Basic)-4.2ChemAxon
Physiological Charge-3ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area140.62 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity68.14 m3·mol-1ChemAxon
Polarizability14.23 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as tricarboxylic acids and derivatives. These are carboxylic acids containing exactly three carboxyl groups.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Tricarboxylic acids and derivatives
Direct Parent
Tricarboxylic acids and derivatives
Alternative Parents
Tertiary alcohols / Carboxylic acid salts / Carboxylic acids / Organic sodium salts / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Tricarboxylic acid or derivatives / Tertiary alcohol / Carboxylic acid salt / Organic alkali metal salt / Carboxylic acid / Organic oxygen compound / Organic oxide / Hydrocarbon derivative / Organic sodium salt / Organic salt
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
organic sodium salt (CHEBI:53258)

Transporters

Kind
Protein
Organism
Homo sapiens
Pharmacological action
No
Actions
Substrate
General Function
Dicarboxylic acid transmembrane transporter activity
Specific Function
Transports C5-C7 oxodicarboxylates across the inner membranes of mitochondria. Can transport 2-oxoadipate, 2-oxoglutarate, adipate, glutarate, and to a lesser extent, pimelate, 2-oxopimelate, 2-ami...
Gene Name
SLC25A21
Uniprot ID
Q9BQT8
Uniprot Name
Mitochondrial 2-oxodicarboxylate carrier
Molecular Weight
33302.88 Da
References
  1. UniProt: Mitochondrial 2-oxodicarboxylate carrier [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Low-affinity sodium:dicarboxylate symporter activity
Specific Function
Cotransport of sodium ions and dicarboxylates such as succinate and citrate.
Gene Name
SLC13A2
Uniprot ID
Q13183
Uniprot Name
Solute carrier family 13 member 2
Molecular Weight
64409.495 Da
References
  1. UniProt: Solute carrier family 13 member 2 [Link]
Kind
Protein
Organism
Homo sapiens
Pharmacological action
No
Actions
Substrate
General Function
Succinate transmembrane transporter activity
Specific Function
High-affinity sodium/citrate cotransporter that mediates citrate entry into cells. The transport process is electrogenic; it is the trivalent form of citrate rather than the divalent form that is r...
Gene Name
SLC13A5
Uniprot ID
Q86YT5
Uniprot Name
Solute carrier family 13 member 5
Molecular Weight
63061.605 Da
References
  1. Inoue K, Zhuang L, Maddox DM, Smith SB, Ganapathy V: Structure, function, and expression pattern of a novel sodium-coupled citrate transporter (NaCT) cloned from mammalian brain. J Biol Chem. 2002 Oct 18;277(42):39469-76. Epub 2002 Aug 11. [PubMed:12177002]
Kind
Protein
Organism
Homo sapiens
Pharmacological action
No
Actions
Substrate
General Function
Tricarboxylic acid transmembrane transporter activity
Specific Function
Involved in citrate-H(+)/malate exchange. Important for the bioenergetics of hepatic cells as it provides a carbon source for fatty acid and sterol biosyntheses, and NAD(+) for the glycolytic pathway.
Gene Name
SLC25A1
Uniprot ID
P53007
Uniprot Name
Tricarboxylate transport protein, mitochondrial
Molecular Weight
34012.46 Da
References
  1. Sun J, Aluvila S, Kotaria R, Mayor JA, Walters DE, Kaplan RS: Mitochondrial and Plasma Membrane Citrate Transporters: Discovery of Selective Inhibitors and Application to Structure/Function Analysis. Mol Cell Pharmacol. 2010;2(3):101-110. [PubMed:20686672]

Drug created on October 01, 2015 14:41 / Updated on September 22, 2018 22:37