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Identification
NameCefixime
Accession NumberDB00671  (APRD00583)
Typesmall molecule
Groupsapproved
Description

Cefixime, an antibiotic, is a third-generation cephalosporin like ceftriaxone and cefotaxime. Cefixime is highly stable in the presence of beta-lactamase enzymes. As a result, many organisms resistant to penicillins and some cephalosporins due to the presence of beta-lactamases, may be susceptible to cefixime. The antibacterial effect of cefixime results from inhibition of mucopeptide synthesis in the bacterial cell wall.

Structure
Thumb
Synonyms
SynonymLanguageCode
(-)-CefiximNot AvailableNot Available
CefiximGermanINN
CefiximaSpanishINN
CéfiximeFrenchINN
CefiximumLatinINN
SaltsNot Available
Brand names
NameCompany
CefixoralMenarini
CefspanGlaxoSmithKline
CephoralMerck
FixamSolas
FixsporInvision
HifenHetero
InfectoOpticefInfectopharm
KuracefSanofi-Aventis
LetixAdley
OfexDelta
Omnatax-OAbbott
OracefMicro Labs
OrokenSanofi Aventis
SancefixSandoz
SecefNovartis
SupranTeva
SupraxSanofi Aventis
Suprax 125Lupin
TricefMerck
UniximeFirma
Uro-CephoralMerck
Brand mixtures
Brand NameIngredients
Fixx ClavCefixime and Clavulanic Acid
Starfix-OFCefixime and Ofloxacin
Categories
CAS number79350-37-1
WeightAverage: 453.45
Monoisotopic: 453.041289239
Chemical FormulaC16H15N5O7S2
InChI KeyOKBVVJOGVLARMR-QSWIMTSFSA-N
InChI
InChI=1S/C16H15N5O7S2/c1-2-6-4-29-14-10(13(25)21(14)11(6)15(26)27)19-12(24)9(20-28-3-8(22)23)7-5-30-16(17)18-7/h2,5,10,14H,1,3-4H2,(H2,17,18)(H,19,24)(H,22,23)(H,26,27)/b20-9-/t10-,14-/m1/s1
IUPAC Name
(6R,7R)-7-[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-[(carboxymethoxy)imino]acetamido]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
SMILES
[H][C@]12SCC(C=C)=C(N1C(=O)[C@H]2NC(=O)C(=N/OCC(O)=O)\C1=CSC(N)=N1)C(O)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassLactams
SubclassBeta Lactams
Direct parentCephalosporins
Alternative parentsN-acyl-alpha Amino Acids and Derivatives; Alpha Amino Acid Amides; 2,4-disubstituted Thiazoles; Primary Aromatic Amines; 1,3-Thiazines; Dicarboxylic Acids and Derivatives; Aminothiazoles; Tertiary Carboxylic Acid Amides; Hemiaminals; Secondary Carboxylic Acid Amides; Oxime Ethers; Polyols; Azetidines; Tertiary Amines; Polyamines; Enamines; Enolates; Aminals; Thioethers; Carboxylic Acids; Imines
Substituentsn-acyl-alpha amino acid or derivative; alpha-amino acid amide; alpha-amino acid or derivative; 2,4-disubstituted 1,3-thiazole; dicarboxylic acid derivative; 1,3-thiazolamine; primary aromatic amine; meta-thiazine; azole; thiazole; tertiary carboxylic acid amide; carboxamide group; azetidine; polyol; hemiaminal; secondary carboxylic acid amide; oxime ether; tertiary amine; carboxylic acid; polyamine; aminal; enamine; enolate; thioether; carboxylic acid derivative; amine; primary amine; organonitrogen compound; imine
Classification descriptionThis compound belongs to the cephalosporins. These are compounds containing a 1,2-thiazine fused to a 2-azetidinone to for a oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid moeity or a derivative thereof.
Pharmacology
IndicationFor use in the treatment of the following infections when caused by susceptible strains of the designated microorganisms: (1) uncomplicated urinary tract infections caused by Escherichia coli and Proteus mirabilis, (2) otitis media caused by Haemophilus influenzae (beta-lactamase positive and negative strains), Moraxella catarrhalis (most of which are beta-lactamase positive), and S. pyogenes, (3) pharyngitis and tonsillitis caused by S. pyogenes, (4) acute bronchitis and acute exacerbations of chronic bronchitis caused by Streptococcus pneumoniae and Haemophilus influenzae (beta-lactamase positive and negative strains), and (5) uncomplicated gonorrhea (cervical/urethral) caused by Neisseria gonorrhoeae (penicillinase- and non-penicillinase-producing strains).
PharmacodynamicsCefixime, an antibiotic, is a third-generation cephalosporin like ceftriaxone and cefotaxime. Cefixime is highly stable in the presence of beta-lactamase enzymes. As a result, many organisms resistant to penicillins and some cephalosporins due to the presence of beta-lactamases, may be susceptible to cefixime. The antibacterial effect of cefixime results from inhibition of mucopeptide synthesis in the bacterial cell wall.
Mechanism of actionLike all beta-lactam antibiotics, cefixime binds to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, causing the inhibition of the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cefixime interferes with an autolysin inhibitor.
AbsorptionAbout 40%-50% absorbed orally whether administered with or without food, however, time to maximal absorption is increased approximately 0.8 hours when administered with food.
Volume of distributionNot Available
Protein binding65% (concentration independent)
Metabolism

Hepatic. Approximately 50% of the absorbed dose is excreted unchanged in the urine in 24 hours.

Route of eliminationNot Available
Half life3-4 hours (may range up to 9 hours). In severe renal impairment (5 to 20 mL/min creatinine clearance), the half-life increased to an average of 11.5 hours.
ClearanceNot Available
ToxicitySymptoms of overdose include blood in the urine, diarrhea, nausea, upper abdominal pain, and vomiting.
Affected organisms
  • Enteric bacteria and other eubacteria
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption - 0.7776
Blood Brain Barrier - 0.9704
Caco-2 permeable - 0.7432
P-glycoprotein substrate Substrate 0.6934
P-glycoprotein inhibitor I Non-inhibitor 0.8863
P-glycoprotein inhibitor II Non-inhibitor 0.8724
Renal organic cation transporter Non-inhibitor 0.8301
CYP450 2C9 substrate Non-substrate 0.9002
CYP450 2D6 substrate Non-substrate 0.8161
CYP450 3A4 substrate Non-substrate 0.5
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.907
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Non-inhibitor 0.8309
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9029
Ames test Non AMES toxic 0.7495
Carcinogenicity Non-carcinogens 0.8549
Biodegradation Not ready biodegradable 0.9911
Rat acute toxicity 1.6878 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9897
hERG inhibition (predictor II) Non-inhibitor 0.895
Pharmacoeconomics
Manufacturers
  • Lederle laboratories div american cyanamid co
  • Lupin pharmaceuticals inc
  • Lupin ltd
Packagers
Dosage forms
FormRouteStrength
Powder, for suspensionOral
TabletOral
Prices
Unit descriptionCostUnit
Suprax 400 mg Tablet3.86USDtablet
Suprax 100 mg/5ml Suspension2.8USDml
Suprax 20 mg/ml Suspension0.45USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point218-225 °CNot Available
water solubility55.11 mg/LNot Available
logP-0.4Not Available
Predicted Properties
PropertyValueSource
water solubility1.04e-01 g/lALOGPS
logP0.25ALOGPS
logP-1.2ChemAxon
logS-3.6ALOGPS
pKa (strongest acidic)3.45ChemAxon
pKa (strongest basic)2.92ChemAxon
physiological charge-2ChemAxon
hydrogen acceptor count10ChemAxon
hydrogen donor count4ChemAxon
polar surface area184.51ChemAxon
rotatable bond count8ChemAxon
refractivity104.91ChemAxon
polarizability41.62ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Pandurang Deshpande, “Process for the preparation of cefixime.” U.S. Patent US20040082560, issued April 29, 2004.

US20040082560
General Reference
  1. McMillan A, Young H: The treatment of pharyngeal gonorrhoea with a single oral dose of cefixime. Int J STD AIDS. 2007 Apr;18(4):253-4. Pubmed
  2. Adam D, Hostalek U, Troster K: 5-day cefixime therapy for bacterial pharyngitis and/or tonsillitis: comparison with 10-day penicillin V therapy. Cefixime Study Group. Infection. 1995;23 Suppl 2:S83-6. Pubmed
External Links
ResourceLink
KEGG DrugD00258
KEGG CompoundC06881
ChEBI472657
ChEMBLCHEMBL1541
Therapeutic Targets DatabaseDAP000439
PharmGKBPA164768821
Drug Product Database2195992
RxListhttp://www.rxlist.com/cgi/generic/cefixime.htm
Drugs.comhttp://www.drugs.com/cdi/cefixime.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/sup1416.shtml
WikipediaCefixime
ATC CodesJ01DD08
AHFS Codes
  • 08:12.06.12
PDB EntriesNot Available
FDA labelshow(3.07 MB)
MSDSshow(43.7 KB)
Interactions
Drug Interactions
Drug
ProbenecidProbenecid may increase the serum level of cefixime.
Food Interactions
  • Preferably on an empty stomach, rate of absorption is decreased but extenet of absorption remains the same: not really problematic.

Targets

1. Penicillin-binding protein 2

Kind: protein

Organism: Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Penicillin-binding protein 2 P44469 Details

References:

  1. Takahata S, Senju N, Osaki Y, Yoshida T, Ida T: Amino acid substitutions in mosaic penicillin-binding protein 2 associated with reduced susceptibility to cefixime in clinical isolates of Neisseria gonorrhoeae. Antimicrob Agents Chemother. 2006 Nov;50(11):3638-45. Epub 2006 Aug 28. Pubmed
  2. Zhao S, Duncan M, Tomberg J, Davies C, Unemo M, Nicholas RA: Genetics of chromosomally mediated intermediate resistance to ceftriaxone and cefixime in Neisseria gonorrhoeae. Antimicrob Agents Chemother. 2009 Sep;53(9):3744-51. Epub 2009 Jun 15. Pubmed

Transporters

1. Solute carrier family 22 member 5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 5 O76082 Details

References:

  1. Ganapathy ME, Huang W, Rajan DP, Carter AL, Sugawara M, Iseki K, Leibach FH, Ganapathy V: beta-lactam antibiotics as substrates for OCTN2, an organic cation/carnitine transporter. J Biol Chem. 2000 Jan 21;275(3):1699-707. Pubmed

2. Solute carrier family 15 member 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Solute carrier family 15 member 1 P46059 Details

References:

  1. Wenzel U, Gebert I, Weintraut H, Weber WM, Clauss W, Daniel H: Transport characteristics of differently charged cephalosporin antibiotics in oocytes expressing the cloned intestinal peptide transporter PepT1 and in human intestinal Caco-2 cells. J Pharmacol Exp Ther. 1996 May;277(2):831-9. Pubmed
  2. Ganapathy ME, Prasad PD, Mackenzie B, Ganapathy V, Leibach FH: Interaction of anionic cephalosporins with the intestinal and renal peptide transporters PEPT 1 and PEPT 2. Biochim Biophys Acta. 1997 Mar 13;1324(2):296-308. Pubmed
  3. 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
  4. Terada T, Saito H, Mukai M, Inui K: Characterization of stably transfected kidney epithelial cell line expressing rat H+/peptide cotransporter PEPT1: localization of PEPT1 and transport of beta-lactam antibiotics. J Pharmacol Exp Ther. 1997 Jun;281(3):1415-21. Pubmed
  5. Terada T, Saito H, Mukai M, Inui K: Recognition of beta-lactam antibiotics by rat peptide transporters, PEPT1 and PEPT2, in LLC-PK1 cells. Am J Physiol. 1997 Nov;273(5 Pt 2):F706-11. Pubmed
  6. Tsuji A: Transporter-mediated Drug Interactions. Drug Metab Pharmacokinet. 2002;17(4):253-74. Pubmed
  7. Tamai I, Nakanishi T, Hayashi K, Terao T, Sai Y, Shiraga T, Miyamoto K, Takeda E, Higashida H, Tsuji A: The predominant contribution of oligopeptide transporter PepT1 to intestinal absorption of beta-lactam antibiotics in the rat small intestine. J Pharm Pharmacol. 1997 Aug;49(8):796-801. Pubmed

3. Solute carrier family 15 member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 15 member 2 Q16348 Details

References:

  1. Ganapathy ME, Prasad PD, Mackenzie B, Ganapathy V, Leibach FH: Interaction of anionic cephalosporins with the intestinal and renal peptide transporters PEPT 1 and PEPT 2. Biochim Biophys Acta. 1997 Mar 13;1324(2):296-308. Pubmed
  2. Terada T, Saito H, Mukai M, Inui K: Recognition of beta-lactam antibiotics by rat peptide transporters, PEPT1 and PEPT2, in LLC-PK1 cells. Am J Physiol. 1997 Nov;273(5 Pt 2):F706-11. Pubmed
  3. 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

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Drug created on June 13, 2005 07:24 / Updated on January 15, 2014 10:52