Chloramphenicol succinate

Identification

Summary

Chloramphenicol succinate is a broad-spectrum antibiotic agent used for the treatment of acute and severe infections caused by susceptible bacterial strains.

Generic Name
Chloramphenicol succinate
DrugBank Accession Number
DB07565
Background

Chloramphenicol succinate is an ester prodrug of chloramphenicol.2 Chloramphenicol is a bacteriostatic antibiotic.5 Use of chloramphenicol succinate and chloramphenicol has decreased due to the risk of potentially fatal blood dyscrasias.10

Chloramphenicol succinate was granted FDA approval on 20 February 1959.9

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 423.202
Monoisotopic: 422.028370912
Chemical Formula
C15H16Cl2N2O8
Synonyms
  • Chloramphenicol hemisuccinate

Pharmacology

Indication

Chloramphenicol succinate is indicated to treat serious and susceptible bacterial infections where less dangerous drugs are ineffective or contraindicated.9

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Chloramphenicol succinate is a prodrug of chloramphenicol, which binds to bacterial ribosomes and prevents translation.1,6,7 It has a narrow therapeutic index8 and a moderate duration of action.10 Patients should be counselled regarding the risk of serious fatal blood dyscrasias.10

Mechanism of action

Chloramphenicol succinate is hydrolyzed into the active chloramphenicol.1 Chloramphenicol resembles uridine-5'-phosphate.6 It binds to the residues A2451 and A2452 in the 23S rRNA of the 50S ribosomal subunit of E. coli, which prevents translation.7

TargetActionsOrganism
UDr hemagglutinin structural subunit
inhibitor
Escherichia coli
Absorption

Chloramphenicol succinate has a high degree of interpatient variability, with a Tmax of 18 minutes to 3 hours.2 A 1g oral chloramphenicol succinate dose every 6-8 hours reaches a mean Cmax of 11.2µg/mL with a Tmax of 1 hour.10

Volume of distribution

Chloramphenicol succinate has a volume of distribution of 0.2-3.1L/kg.2

Protein binding

Chloramphenicol succinate is 57-92% protein bound in plasma.2

Metabolism

Chloramphenicol succinate is hydrolyzed to chloramphenicol.1 The propane-diol moiety of chloramphenicol can be metabolised through a number of pathways including glucuronidation, sulfate conjugation, phosphorylation, acetylation, and oxidation.4 The dichloroacetate moiety can be metabolised through hydrolysis of the amide group and dechlorination.4 The nitro functional group can also be metabolised to an aryl amine and aryl amide metabolite.4

Hover over products below to view reaction partners

Route of elimination

6-80% of chloramphenicol succinate is eliminated unchanged in the urine, though this is highly variable between patients.2 On average, 30% of chloramphenicol succinate is eliminated unchanged in the urine and 10% is eliminated as the active chloramphenicol in the urine.2

Half-life

The half life of chloramphenicol succinate in patients with normal renal and hepatic function is 0.6-2.7h.2

Clearance

Chloramphenicol succinate's total clearance is 530-540mL/min in patients with normal renal and hepatic function, and 354mL/min in patients with renal or hepatic dysfunction.2 Chloramphenicol succinate's renal clearance is 222-260mL/min in patients with normal renal and hepatic function, and 66mL/min in patients with renal or hepatic dysfunction.2

Adverse Effects
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Toxicity

Patients experiencing an overdose may present with shock, cyanosis, and coma.3 Treat patients with symptomatic and supportive measures which may include administration of fluids, exchange transfusions, and administration of dopamine.3

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcenocoumarolThe risk or severity of bleeding can be increased when Chloramphenicol succinate is combined with Acenocoumarol.
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Chloramphenicol succinate.
DicoumarolThe risk or severity of bleeding can be increased when Chloramphenicol succinate is combined with Dicoumarol.
EstetrolThe therapeutic efficacy of Estetrol can be decreased when used in combination with Chloramphenicol succinate.
FluindioneThe risk or severity of bleeding can be increased when Chloramphenicol succinate is combined with Fluindione.
PhenindioneThe risk or severity of bleeding can be increased when Chloramphenicol succinate is combined with Phenindione.
PhenprocoumonThe risk or severity of bleeding can be increased when Chloramphenicol succinate is combined with Phenprocoumon.
Typhoid vaccineThe therapeutic efficacy of Typhoid vaccine can be decreased when used in combination with Chloramphenicol succinate.
Vibrio cholerae CVD 103-HgR strain live antigenThe therapeutic efficacy of Vibrio cholerae CVD 103-HgR strain live antigen can be decreased when used in combination with Chloramphenicol succinate.
WarfarinThe risk or severity of bleeding can be increased when Chloramphenicol succinate is combined with Warfarin.
Interactions
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Food Interactions
No interactions found.

Products

Products
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Product Ingredients
IngredientUNIICASInChI Key
Chloramphenicol sodium succinate872109HX6B982-57-0RPLOPBHEZLFENN-HTMVYDOJSA-M
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Chloromycetin Sodium SuccinateInjection100 mg/1mLIntravenousMonarch Pharmaceuticals, Inc.1959-02-202007-10-05US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Chloramphenicol Sodium SuccinateInjection, powder, lyophilized, for solution1 g/10mLIntravenousFresenius Kabi USA, LLC2001-01-12Not applicableUS flag
Chloramphenicol Sodium SuccinateInjection, powder, lyophilized, for solution1 g/10mLIntravenousGeneral Injectables & Vaccines2010-09-012017-01-18US flag

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as nitrobenzenes. These are compounds containing a nitrobenzene moiety, which consists of a benzene ring with a carbon bearing a nitro group.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Nitrobenzenes
Direct Parent
Nitrobenzenes
Alternative Parents
Nitroaromatic compounds / Fatty acid esters / Dicarboxylic acids and derivatives / Secondary carboxylic acid amides / Secondary alcohols / Carboxylic acid esters / Propargyl-type 1,3-dipolar organic compounds / Carboxylic acids / Organic oxoazanium compounds / Organic oxides
show 8 more
Substituents
Alcohol / Alkyl chloride / Alkyl halide / Allyl-type 1,3-dipolar organic compound / Aromatic alcohol / Aromatic homomonocyclic compound / C-nitro compound / Carbonyl group / Carboxamide group / Carboxylic acid
show 23 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available
Affected organisms
  • Gram negative and gram positive bacteria

Chemical Identifiers

UNII
ZCX619U9A1
CAS number
3544-94-3
InChI Key
LIRCDOVJWUGTMW-ZWNOBZJWSA-N
InChI
InChI=1S/C15H16Cl2N2O8/c16-14(17)15(24)18-10(7-27-12(22)6-5-11(20)21)13(23)8-1-3-9(4-2-8)19(25)26/h1-4,10,13-14,23H,5-7H2,(H,18,24)(H,20,21)/t10-,13-/m1/s1
IUPAC Name
4-[(2R,3R)-2-(2,2-dichloroacetamido)-3-hydroxy-3-(4-nitrophenyl)propoxy]-4-oxobutanoic acid
SMILES
O[C@@H]([C@@H](COC(=O)CCC(O)=O)NC(=O)C(Cl)Cl)C1=CC=C(C=C1)[N+]([O-])=O

References

General References
  1. Borde AS, Karlsson EM, Andersson K, Bjorhall K, Lennernas H, Abrahamsson B: Assessment of enzymatic prodrug stability in human, dog and simulated intestinal fluids. Eur J Pharm Biopharm. 2012 Apr;80(3):630-7. doi: 10.1016/j.ejpb.2011.11.011. Epub 2011 Dec 4. [Article]
  2. Ambrose PJ: Clinical pharmacokinetics of chloramphenicol and chloramphenicol succinate. Clin Pharmacokinet. 1984 May-Jun;9(3):222-38. doi: 10.2165/00003088-198409030-00004. [Article]
  3. Thompson WL, Anderson SE, Lipsky JJ, Lietman PS: Letter: Overdoses of chloramphenicol. JAMA. 1975 Oct 13;234(2):149-50. [Article]
  4. Bories GF, Cravedi JP: Metabolism of chloramphenicol: a story of nearly 50 years. Drug Metab Rev. 1994;26(4):767-83. doi: 10.3109/03602539408998326. [Article]
  5. Loree J, Lappin SL: Bacteriostatic Antibiotics . [Article]
  6. Jardetzky O: Studies on the Mechanism of Action of Chloramphenicol The Journal of Biological Chemistry. 1963 July;238(7):2498-2508. [Article]
  7. Schifano JM, Edifor R, Sharp JD, Ouyang M, Konkimalla A, Husson RN, Woychik NA: Mycobacterial toxin MazF-mt6 inhibits translation through cleavage of 23S rRNA at the ribosomal A site. Proc Natl Acad Sci U S A. 2013 May 21;110(21):8501-6. doi: 10.1073/pnas.1222031110. Epub 2013 May 6. [Article]
  8. Wiest DB, Cochran JB, Tecklenburg FW: Chloramphenicol toxicity revisited: a 12-year-old patient with a brain abscess. J Pediatr Pharmacol Ther. 2012 Apr;17(2):182-8. doi: 10.5863/1551-6776-17.2.182. [Article]
  9. FDA Approved Drug Products: Chloramphenicol Sodium Succinate Intravenous Injection [Link]
  10. DailyMed: Chloramphenicol Succinate Powder for Injection [Link]
KEGG Compound
C11727
PubChem Compound
656580
PubChem Substance
99444036
ChemSpider
570947
RxNav
20769
ChEBI
3606
ChEMBL
CHEMBL1201281
ZINC
ZINC000001532336
PDBe Ligand
CL8
Wikipedia
Chloramphenicol
PDB Entries
2jkn / 2w5p

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous1 g/10mL
Powder1000 mg/1vial
InjectionIntravenous100 mg/1mL
Capsule
Injection, powder, for solutionIntravenous1 G
Injection, powder, lyophilized, for solutionIntravenous
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.112 mg/mLALOGPS
logP1.34ALOGPS
logP1.14ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)3.65ChemAxon
pKa (Strongest Basic)-3.4ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area156.07 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity92.24 m3·mol-1ChemAxon
Polarizability37.74 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.6818
Blood Brain Barrier+0.9097
Caco-2 permeable-0.5067
P-glycoprotein substrateNon-substrate0.6633
P-glycoprotein inhibitor INon-inhibitor0.7924
P-glycoprotein inhibitor IINon-inhibitor0.8358
Renal organic cation transporterNon-inhibitor0.923
CYP450 2C9 substrateNon-substrate0.8336
CYP450 2D6 substrateNon-substrate0.8552
CYP450 3A4 substrateNon-substrate0.5375
CYP450 1A2 substrateNon-inhibitor0.6683
CYP450 2C9 inhibitorInhibitor0.5155
CYP450 2D6 inhibitorNon-inhibitor0.8638
CYP450 2C19 inhibitorInhibitor0.797
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6768
Ames testNon AMES toxic0.9159
CarcinogenicityNon-carcinogens0.7575
BiodegradationNot ready biodegradable0.6038
Rat acute toxicity1.9742 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9022
hERG inhibition (predictor II)Non-inhibitor0.781
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets
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Kind
Protein
Organism
Escherichia coli
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Not Available
Specific Function
Hemagglutinins of uropathogenic E.coli mediate adherence to the upper urinary tract. These adhesins bind to the Dr blood group antigen and also agglutinate human erythrocytes in the presence of D-m...
Gene Name
draA
Uniprot ID
P24093
Uniprot Name
Dr hemagglutinin structural subunit
Molecular Weight
17058.095 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]

Enzymes

Kind
Protein
Organism
Escherichia coli
Pharmacological action
Unknown
Actions
Substrate
General Function
Chloramphenicol o-acetyltransferase activity
Specific Function
This enzyme is an effector of chloramphenicol resistance in bacteria.
Gene Name
cat3
Uniprot ID
P00484
Uniprot Name
Chloramphenicol acetyltransferase 3
Molecular Weight
24993.32 Da
References
  1. Shaw WV: Chloramphenicol acetyltransferase: enzymology and molecular biology. CRC Crit Rev Biochem. 1983;14(1):1-46. doi: 10.3109/10409238309102789. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Vodrazka Z, Jandova D, Grafnetterova J, Schuck O, Kalousek I, Tomaasek R, Lachmanova J: The binding of chloramphenicol to albumin of normal and uremic sera. Biochem Pharmacol. 1978;27(13):1717-20. doi: 10.1016/0006-2952(78)90545-2. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Nurbaeti SN, Olivier JC, Adier C, Marchand S, Couet W, Brillault J: Active Mediated Transport of Chloramphenicol and Thiamphenicol in a Calu-3 Lung Epithelial Cell Model. J Pharm Sci. 2018 Apr;107(4):1178-1184. doi: 10.1016/j.xphs.2017.11.021. Epub 2017 Dec 5. [Article]

Drug created on September 15, 2010 21:23 / Updated on May 07, 2021 21:43