DrugBank: Ceftriaxone (DB01212)

targets (1) transporters (5) carriers (1)

Identification

Name

Ceftriaxone

Accession Number

DB01212 (APRD00395)

Type

small molecule

Groups

approved

Description

A broad-spectrum cephalosporin antibiotic with a very long half-life and high penetrability to meninges, eyes and inner ears. [PubChem]

Structure

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Cefatriaxone
Ceftriaxona [INN-Spanish]
Ceftriaxonum [INN-Latin]
Ceftriazone

Brand names

Biotrakson
Rocephine

Brand name mixtures

Not Available

Categories

Anti-Bacterial Agents
Cephalosporins

CAS number

73384-59-5

Weight

Average: 554.58
Monoisotopic: 554.046057040

Chemical Formula

C₁₈H₁₈N₈O₇S₃

InChI Key

InChIKey=VAAUVRVFOQPIGI-SPQHTLEESA-N

InChI

InChI=1S/C18H18N8O7S3/c1-25-18(22-12(28)13(29)23-25)36-4-6-3-34-15-9(14(30)26(15)10(6)16(31)32)21-11(27)8(24-33-2)7-5-35-17(19)20-7/h5,9,15H,3-4H2,1-2H3,(H2,19,20)(H,21,27)(H,23,29)(H,31,32)/b24-8-/t9-,15-/m1/s1

Plain Text

IUPAC Name

(6R,7R)-7-[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetamido]-3-{[(2-methyl-5,6-dioxo-1,2,5,6-tetrahydro-1,2,4-triazin-3-yl)sulfanyl]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

SMILES

[H][C@]12SCC(CSC3=NC(=O)C(=O)NN3C)=C(N1C(=O)[C@H]2NC(=O)C(=N/OC)\C1=CSC(N)=N1)C(O)=O

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Triazines
Cephalosporins

Substructures

Ethers
Hydroxy Compounds
Acetates
Amino Ketones
Oximes and Derivatives
Aliphatic and Aryl Amines
Beta Lactams
Enamines
Thiazoles
Heterocyclic compounds
Aromatic compounds
Carboxamides and Derivatives
Triazines
Cephalosporins
Lactams
Imines
Azetidines
Cyanamides

Pharmacology

Indication

For the treatment of the infections (respiratory, skin, soft tissue, UTI, ENT) caused by S. pneumoniae, H. influenzae, staphylococci, S. pyogenes (group A beta-hemolytic streptococci), E. coli, P. mirabilis, Klebsiella sp, coagulase-negative staph

Pharmacodynamics

Ceftriaxone is a cephalosporin/cephamycin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. Ceftriaxone has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of Ceftriaxone results from the inhibition of cell wall synthesis and is mediated through Ceftriaxone binding to penicillin binding proteins (PBPs). Ceftriaxone is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases.

Mechanism of action

Ceftriaxone works by inhibiting the mucopeptide synthesis in the bacterial cell wall. The beta-lactam moiety of Ceftriaxone binds to carboxypeptidases, endopeptidases, and transpeptidases in the bacterial cytoplasmic membrane. These enzymes are involved in cell-wall synthesis and cell division. By binding to these enzymes, Ceftriaxone results in the formation of of defective cell walls and cell death.

Absorption

Not Available

Volume of distribution

5.78 to 13.5 L

Protein binding

95%

Metabolism

Route of elimination

Thirty-three percent to 67% of a ceftriaxone dose was excreted in the urine as unchanged drug and the remainder was secreted in the bile and ultimately found in the feces as microbiologically inactive compounds.

Half life

5.8-8.7 hours

Clearance

0.58 – 1.45 L/h [healthy adults receiving 0.15-3 g of CEFTRIAXONE]

Toxicity

Not Available

Affected organisms

Enteric bacteria and other eubacteria

Pathways

Not Available

Pharmacoeconomics

Manufacturers

App pharmaceuticals llc
Aurobindo pharma ltd
Bedford laboratories div ben venue laboratories inc
Cephazone pharma llc
Hikma farmaceutica (portugal) sa
Luitpold pharmaceuticals inc
Lupin ltd
Orchid healthcare
Sandoz inc
Steri pharma llc
Teva pharmaceuticals usa inc
Teva parenteral medicines inc
Wockhardt ltd
Acs dobfar spa
B braun medical inc
Baxter healthcare corp
Hoffmann la roche inc

Packagers

Dosage forms

Form	Route	Strength
Powder, for solution	Intravenous

Prices

Unit description	Cost	Unit
Rocephin 10 gm vial	478.32 USD	vial
Rocephin 2 gm vial	97.5 USD	vial
Ceftriaxone 2 gm piggyback	94.17 USD	each
Rocephin 1 gm Solution Vial	65.53 USD	vial
Rocephin 1 gm vial	62.02 USD	vial
Ceftriaxone For Injection Usp 2 g/vial	49.13 USD	vial
Ceftriaxone 1 gm piggyback	47.91 USD	each
Rocephin 1 g/vial	40.2 USD	vial
Ceftriaxone 10 gm vial	36.25 USD	vial
Ceftriaxone 2 gm-d5w bag	27.84 USD	each
Ceftriaxone For Injection Usp 1 g/vial	24.93 USD	vial
Chloromycetin 1 g/vial	20.33 USD	vial
Ceftriaxone 2 gm vial	17.04 USD	vial
Ceftriaxone 1 gm-d5w bag	13.92 USD	each
Rocephin 0.25 g/vial	12.71 USD	vial
Ceftriaxone For Injection Usp 0.25 g/vial	7.88 USD	vial
Ceftriaxone 1 gm vial	7.56 USD	vial
Ceftriaxone sodium powder	1.84 USD	g

Patents

Not Available

Properties

State

solid

Melting point

>155 oC

Experimental Properties

Property	Value	Source
logP	-1.7	PhysProp
Caco2 permeability	-6.88 [ADME Research, USCD]	BiGG

Predicted Properties

Property	Value	Source
water solubility	1.05e-01 g/l	ALOGPS
logP	-0.01	ALOGPS
logP	-1.82	ChemAxon Molconvert
logS	-3.72	ALOGPS
pKa	3.96	ChemAxon Molconvert
hydrogen acceptor count	12	ChemAxon Molconvert
hydrogen donor count	4	ChemAxon Molconvert
polar surface area	208.98	ChemAxon Molconvert
rotatable bond count	8	ChemAxon Molconvert
refractivity	128.47	ChemAxon Molconvert
polarizability	51.47	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
KEGG Compound	C06683
PubChem Compound	5479530
PubChem Substance	46506458
ChemSpider	4514885
ChEBI	29007
ChEMBL	29007
Therapeutic Targets Database	DAP000145
PharmGKB	PA448866
Drug Product Database	657409
RxList	http://www.rxlist.com/cgi/generic3/ceftriax.htm
Drugs.com	http://www.drugs.com/cdi/ceftriaxone.html
Wikipedia	http://en.wikipedia.org/wiki/Ceftriaxone

ATC Codes

J01DD04

AHFS Codes

08:12.06.12

PDB Entries

Not Available

FDA label

show (210.9 KB)

MSDS

show (53.3 KB)

Interactions

Drug Interactions

Not Available

Food Interactions

Not Available

Targets
1. Penicillin-binding protein 2B Pharmacological action: yes Actions: inhibitor Organism class: bacterial UniProt ID: P0A3M6 Gene: penA Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Tomberg J, Unemo M, Davies C, Nicholas RA: Molecular and Structural Analysis of Mosaic Variants of Penicillin-Binding Protein 2 Conferring Decreased Susceptibility to Expanded-Spectrum Cephalosporins in Neisseria gonorrhoeae: Role of Epistatic Mutations. Biochemistry. 2010 Aug 25. Pubmed

Targets

1. Penicillin-binding protein 2B

Pharmacological action: yes
Actions: inhibitor
Organism class: bacterial
UniProt ID: P0A3M6 Link_out

Gene: penA Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Tomberg J, Unemo M, Davies C, Nicholas RA: Molecular and Structural Analysis of Mosaic Variants of Penicillin-Binding Protein 2 Conferring Decreased Susceptibility to Expanded-Spectrum Cephalosporins in Neisseria gonorrhoeae: Role of Epistatic Mutations. Biochemistry. 2010 Aug 25. Pubmed

Transporters
1. Oligopeptide transporter, small intestine isoform Actions: inhibitor Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products UniProt ID: P46059 Gene: SLC15A1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Luckner P, Brandsch M: Interaction of 31 beta-lactam antibiotics with the H+/peptide symporter PEPT2: analysis of affinity constants and comparison with PEPT1. Eur J Pharm Biopharm. 2005 Jan;59(1):17-24. Pubmed 2. Oligopeptide transporter, kidney isoform Actions: inhibitor Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides UniProt ID: Q16348 Gene: SLC15A2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Luckner P, Brandsch M: Interaction of 31 beta-lactam antibiotics with the H+/peptide symporter PEPT2: analysis of affinity constants and comparison with PEPT1. Eur J Pharm Biopharm. 2005 Jan;59(1):17-24. Pubmed 3. Solute carrier family 22 member 6 Actions: inhibitor UniProt ID: Q4U2R8 Gene: hROAT1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Takeda M, Babu E, Narikawa S, Endou H: Interaction of human organic anion transporters with various cephalosporin antibiotics. Eur J Pharmacol. 2002 Mar 8;438(3):137-42. Pubmed Jung KY, Takeda M, Shimoda M, Narikawa S, Tojo A, Kim DK, Chairoungdua A, Choi BK, Kusuhara H, Sugiyama Y, Sekine T, Endou H: Involvement of rat organic anion transporter 3 (rOAT3) in cephaloridine-induced nephrotoxicity: in comparison with rOAT1. Life Sci. 2002 Mar 8;70(16):1861-74. Pubmed Jariyawat S, Sekine T, Takeda M, Apiwattanakul N, Kanai Y, Sophasan S, Endou H: The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1. J Pharmacol Exp Ther. 1999 Aug;290(2):672-7. Pubmed 4. Solute carrier family 22 member 8 Actions: inhibitor Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone- 3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA) UniProt ID: Q8TCC7 Gene: SLC22A8 Protein Sequence: FASTA SNPs: SNPJam Report References: Takeda M, Babu E, Narikawa S, Endou H: Interaction of human organic anion transporters with various cephalosporin antibiotics. Eur J Pharmacol. 2002 Mar 8;438(3):137-42. Pubmed Jung KY, Takeda M, Shimoda M, Narikawa S, Tojo A, Kim DK, Chairoungdua A, Choi BK, Kusuhara H, Sugiyama Y, Sekine T, Endou H: Involvement of rat organic anion transporter 3 (rOAT3) in cephaloridine-induced nephrotoxicity: in comparison with rOAT1. Life Sci. 2002 Mar 8;70(16):1861-74. Pubmed 5. Solute carrier family 22 member 11 Actions: inhibitor Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds UniProt ID: Q9NSA0 Gene: SLC22A11 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Takeda M, Babu E, Narikawa S, Endou H: Interaction of human organic anion transporters with various cephalosporin antibiotics. Eur J Pharmacol. 2002 Mar 8;438(3):137-42. Pubmed

Transporters

1. Oligopeptide transporter, small intestine isoform

Actions: inhibitor

Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products

UniProt ID: P46059 Link_out

Gene: SLC15A1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Luckner P, Brandsch M: Interaction of 31 beta-lactam antibiotics with the H+/peptide symporter PEPT2: analysis of affinity constants and comparison with PEPT1. Eur J Pharm Biopharm. 2005 Jan;59(1):17-24. Pubmed

2. Oligopeptide transporter, kidney isoform

Actions: inhibitor

Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides

UniProt ID: Q16348 Link_out

Gene: SLC15A2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Luckner P, Brandsch M: Interaction of 31 beta-lactam antibiotics with the H+/peptide symporter PEPT2: analysis of affinity constants and comparison with PEPT1. Eur J Pharm Biopharm. 2005 Jan;59(1):17-24. Pubmed

3. Solute carrier family 22 member 6

Actions: inhibitor
UniProt ID: Q4U2R8 Link_out

Gene: hROAT1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Takeda M, Babu E, Narikawa S, Endou H: Interaction of human organic anion transporters with various cephalosporin antibiotics. Eur J Pharmacol. 2002 Mar 8;438(3):137-42. Pubmed
Jung KY, Takeda M, Shimoda M, Narikawa S, Tojo A, Kim DK, Chairoungdua A, Choi BK, Kusuhara H, Sugiyama Y, Sekine T, Endou H: Involvement of rat organic anion transporter 3 (rOAT3) in cephaloridine-induced nephrotoxicity: in comparison with rOAT1. Life Sci. 2002 Mar 8;70(16):1861-74. Pubmed
Jariyawat S, Sekine T, Takeda M, Apiwattanakul N, Kanai Y, Sophasan S, Endou H: The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1. J Pharmacol Exp Ther. 1999 Aug;290(2):672-7. Pubmed

4. Solute carrier family 22 member 8

Actions: inhibitor

Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone- 3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA)

UniProt ID: Q8TCC7 Link_out

Gene: SLC22A8 Link_out

Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Takeda M, Babu E, Narikawa S, Endou H: Interaction of human organic anion transporters with various cephalosporin antibiotics. Eur J Pharmacol. 2002 Mar 8;438(3):137-42. Pubmed
Jung KY, Takeda M, Shimoda M, Narikawa S, Tojo A, Kim DK, Chairoungdua A, Choi BK, Kusuhara H, Sugiyama Y, Sekine T, Endou H: Involvement of rat organic anion transporter 3 (rOAT3) in cephaloridine-induced nephrotoxicity: in comparison with rOAT1. Life Sci. 2002 Mar 8;70(16):1861-74. Pubmed

5. Solute carrier family 22 member 11

Actions: inhibitor

Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds

UniProt ID: Q9NSA0 Link_out

Gene: SLC22A11 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Takeda M, Babu E, Narikawa S, Endou H: Interaction of human organic anion transporters with various cephalosporin antibiotics. Eur J Pharmacol. 2002 Mar 8;438(3):137-42. Pubmed

Carriers
1. Serum albumin Actions: other/unknown 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 colloidal osmotic pressure of blood UniProt ID: P02768 Gene: ALB Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Gulian JM, Dalmasso C, Gonard V: Interaction of beta-lactam antibiotics on bilirubin-albumin complex: comparison by three methods, total bilirubin, unbound bilirubin and erythrocyte-bound bilirubin. Chemotherapy. 1990;36(2):91-7. Pubmed Nerli B, Farruggia B, Pico G: A comparative study of the binding characteristics of ceftriaxone, cefoperazone and cefsulodin to human serum albumin. Biochem Mol Biol Int. 1996 Nov;40(4):823-31. Pubmed Robertson A, Fink S, Karp W: Effect of cephalosporins on bilirubin-albumin binding. J Pediatr. 1988 Feb;112(2):291-4. Pubmed

Carriers

1. Serum albumin

Actions: other/unknown

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 colloidal osmotic pressure of blood

UniProt ID: P02768 Link_out

Gene: ALB

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Gulian JM, Dalmasso C, Gonard V: Interaction of beta-lactam antibiotics on bilirubin-albumin complex: comparison by three methods, total bilirubin, unbound bilirubin and erythrocyte-bound bilirubin. Chemotherapy. 1990;36(2):91-7. Pubmed
Nerli B, Farruggia B, Pico G: A comparative study of the binding characteristics of ceftriaxone, cefoperazone and cefsulodin to human serum albumin. Biochem Mol Biol Int. 1996 Nov;40(4):823-31. Pubmed
Robertson A, Fink S, Karp W: Effect of cephalosporins on bilirubin-albumin binding. J Pediatr. 1988 Feb;112(2):291-4. Pubmed

Comments

Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:09

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.