Identification

Name
Fosfomycin
Accession Number
DB00828  (APRD00987)
Type
Small Molecule
Groups
Approved
Description

An antibiotic produced by Streptomyces fradiae. [PubChem]

Structure
Thumb
Synonyms
  • (-)-(1R,2S)-(1,2-Epoxypropyl)phosphonic acid
  • (1R,2S)-Epoxypropylphosphonic acid
  • (2R-cis)-(3-Methyloxiranyl)phosphonic acid
  • 1R-cis-(1,2-Epoxypropyl)phosphonic acid
  • cis-(1R,2S)-Epoxypropylphosphonic acid
  • FCM
  • Fosfocina
  • Fosfomicina
  • FOSFOMYCIN
  • Fosfomycine
  • Fosfomycinum
  • L-cis-1,2-Epoxypropylphosphonic acid
  • Phosphomycin
  • Phosphonemycin
  • Phosphonomycin
External IDs
J01XX01
Product Ingredients
IngredientUNIICASInChI Key
Fosfomycin calcium monohydrateT330QG2NYS26469-67-0MSHCINMVQZDXTG-JSTPYPERSA-N
Fosfomycin disodium97MMO19FNO26016-99-9QZIQJIKUVJMTDG-UHFFFAOYSA-L
Fosfomycin tromethamine7FXW6U30GY78964-85-9QZJIMDIBFFHQDW-LMLSDSMGSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MonurolPowder3 g/1OralAllergan1996-12-19Not applicableUs
MonurolPowder3 gOralPaladin Labs Inc1999-09-15Not applicableCanada
International/Other Brands
Veramina (Roux-Ocefa)
Categories
UNII
2N81MY12TE
CAS number
23155-02-4
Weight
Average: 138.059
Monoisotopic: 138.008195224
Chemical Formula
C3H7O4P
InChI Key
YMDXZJFXQJVXBF-STHAYSLISA-N
InChI
InChI=1S/C3H7O4P/c1-2-3(7-2)8(4,5)6/h2-3H,1H3,(H2,4,5,6)/t2-,3+/m0/s1
IUPAC Name
[(2R,3S)-3-methyloxiran-2-yl]phosphonic acid
SMILES

Pharmacology

Indication

For the treatment of uncomplicated urinary tract infections (acute cystitis) in women due to susceptible strains of Escherichia coli and Enterococcus faecalis.

Structured Indications
Pharmacodynamics

Fosfomycin is a broad spectrum antibiotic that concentrates in kidney and bladder and is used to treat uncomplicated urinary tract infections. Fosfomycin also reduces nephrotoxicity and ototoxicity of platinum-containing anti-tumor agents.

Mechanism of action

Fosfomycin is a phosphoenolpyruvate analogue produced by Streptomyces that irreversibly inhibits enolpyruvate transferase (MurA), which prevents the formation of N-acetylmuramic acid, an essential element of the peptidoglycan cell wall.

TargetActionsOrganism
AUDP-N-acetylglucosamine 1-carboxyvinyltransferase
inhibitor
Escherichia coli (strain K12)
Absorption

Fosfomycin tromethamine is rapidly absorbed following oral administration and converted to fosfomycin. Oral bioavailability under fasting conditions is 37%. When given with food, oral bioavailability is reduced to 30%

Volume of distribution
  • 136.1 ±44.1 L
Protein binding

0% (not bound to plasma proteins)

Metabolism

No transformation, excreted unchanged

Route of elimination

Fosfomycin is excreted unchanged in both urine and feces.

Half life

5.7 (± 2.8) hours. The elimination half-life is 40 hours in anuric patients undergoing hemodialysis.

Clearance
  • 16.9 +/- 3.5 L/hr
Toxicity

LD50>5 g/kg (rats). Side effects may include diarrhea

Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Fosfomycin.Investigational
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Fosfomycin.Approved
Food Interactions
  • Food decreases Cmax slightly.
  • Take without regard to meals.

References

Synthesis Reference

Graziano Castaldi, Claudio Giordano, "Process for the preparation of intermediates for the synthesis of fosfomycin." U.S. Patent US4937367, issued March, 1972.

US4937367
General References
Not Available
External Links
Human Metabolome Database
HMDB14966
KEGG Drug
D04253
KEGG Compound
C06454
PubChem Compound
446987
PubChem Substance
46506665
ChemSpider
394204
BindingDB
50024894
ChEBI
28915
ChEMBL
CHEMBL1757
Therapeutic Targets Database
DAP000767
PharmGKB
PA164748039
HET
FCN
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Fosfomycin
ATC Codes
J01XX01 — Fosfomycin
AHFS Codes
  • 08:36.00 — Urinary Anti-infectives
PDB Entries
1lqp / 2bnn / 3d41 / 3quo / 4ir0 / 4jd1 / 4jh3 / 4jh4 / 4jh5 / 4jh6
show 2 more
FDA label
Download (267 KB)
MSDS
Download (61.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
1CompletedNot AvailableHealthy Volunteers1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedTreatmentPseudomonas Infections1
2CompletedTreatmentFibromyalgia / Iron Deficiency1
2CompletedTreatmentIron Deficiency Anemia (IDA)1
2CompletedTreatmentRestless Legs Syndrome (RLS)2
2Unknown StatusTreatmentIron Deficiency Anemia (IDA)2
3CompletedTreatmentAnemias5
3CompletedTreatmentImpaired Renal Function / Iron Deficiency Anemia (IDA)1
3CompletedTreatmentIron Deficiency Anemia (IDA)1
3CompletedTreatmentPostpartum Anemia1
3RecruitingTreatmentGonorrhea1
4Active Not RecruitingTreatmentCystitis / Urinary Tract Infections (UTIs)1
4Active Not RecruitingTreatmentIron Deficiency Anemia (IDA)1
4Active Not RecruitingTreatmentIron Deficiency Anemia (IDA) Secondary to Inflammatory Bowel Disease (IBD) or Gastric Bypass1
4CompletedPreventionAsymptomatic Bacteriuria / Urinary Tract Infections (UTIs)1
4CompletedPreventionUrinary Tract Infections (UTIs)1
4Not Yet RecruitingTreatmentProsthetic Joint Infection1
4RecruitingTreatmentHeart Failure With Reduced Ejection Fraction (HFrEF) / Iron Deficiency1
4RecruitingTreatmentUrinary Tract Infections (UTIs)1
4Unknown StatusTreatmentInfective Endocarditis1
Not AvailableActive Not RecruitingTreatmentUrinary Tract Infections (UTIs)1
Not AvailableRecruitingNot AvailableUrinary Tract Infections (UTIs)1

Pharmacoeconomics

Manufacturers
  • Zambon spa italy
Packagers
Dosage forms
FormRouteStrength
PowderOral3 g/1
PowderOral3 g
Prices
Unit descriptionCostUnit
Monurol 3 gm Packets50.87USD packet
Monurol 3 gm sachet47.07USD each
Viramune 200 mg tablet9.48USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)94 °CPhysProp
water solubility50 mg/mL (Sodium salt)Not Available
logP-1.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility46.9 mg/mLALOGPS
logP-0.86ALOGPS
logP-0.74ChemAxon
logS-0.47ALOGPS
pKa (Strongest Acidic)1.25ChemAxon
pKa (Strongest Basic)-4.3ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area70.06 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity25.87 m3·mol-1ChemAxon
Polarizability10.8 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.5
Blood Brain Barrier+0.9382
Caco-2 permeable-0.6652
P-glycoprotein substrateNon-substrate0.7234
P-glycoprotein inhibitor INon-inhibitor0.8938
P-glycoprotein inhibitor IINon-inhibitor0.9878
Renal organic cation transporterNon-inhibitor0.9505
CYP450 2C9 substrateNon-substrate0.7514
CYP450 2D6 substrateNon-substrate0.8332
CYP450 3A4 substrateNon-substrate0.6513
CYP450 1A2 substrateNon-inhibitor0.8492
CYP450 2C9 inhibitorNon-inhibitor0.8551
CYP450 2D6 inhibitorNon-inhibitor0.9202
CYP450 2C19 inhibitorNon-inhibitor0.8016
CYP450 3A4 inhibitorNon-inhibitor0.9624
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.944
Ames testNon AMES toxic0.6575
CarcinogenicityNon-carcinogens0.6059
BiodegradationNot ready biodegradable0.894
Rat acute toxicity2.5802 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9456
hERG inhibition (predictor II)Non-inhibitor0.9491
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
GC-MS Spectrum - GC-MS (2 TMS)GC-MSsplash10-03di-2980000000-005d5b96a1e9219362d0
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - GC-MSGC-MSsplash10-03di-2980000000-005d5b96a1e9219362d0
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as organic phosphonic acids. These are organic compounds containing phosphonic acid.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Organic phosphonic acids and derivatives
Sub Class
Organic phosphonic acids
Direct Parent
Organic phosphonic acids
Alternative Parents
Oxacyclic compounds / Epoxides / Organopnictogen compounds / Organophosphorus compounds / Organooxygen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
Organophosphonic acid / Oxacycle / Organoheterocyclic compound / Oxirane / Organic oxygen compound / Organopnictogen compound / Organic oxide / Hydrocarbon derivative / Organophosphorus compound / Organooxygen compound
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
epoxide, phosphonic acids (CHEBI:28915) / Aliphatic compounds (C06454)

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Udp-n-acetylglucosamine 1-carboxyvinyltransferase activity
Specific Function
Cell wall formation. Adds enolpyruvyl to UDP-N-acetylglucosamine. Target for the antibiotic fosfomycin.
Gene Name
murA
Uniprot ID
P0A749
Uniprot Name
UDP-N-acetylglucosamine 1-carboxyvinyltransferase
Molecular Weight
44817.24 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Kim DH, Lees WJ, Kempsell KE, Lane WS, Duncan K, Walsh CT: Characterization of a Cys115 to Asp substitution in the Escherichia coli cell wall biosynthetic enzyme UDP-GlcNAc enolpyruvyl transferase (MurA) that confers resistance to inactivation by the antibiotic fosfomycin. Biochemistry. 1996 Apr 16;35(15):4923-8. [PubMed:8664284]
  4. Eschenburg S, Priestman M, Schonbrunn E: Evidence that the fosfomycin target Cys115 in UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) is essential for product release. J Biol Chem. 2005 Feb 4;280(5):3757-63. Epub 2004 Nov 5. [PubMed:15531591]
  5. McCoy AJ, Sandlin RC, Maurelli AT: In vitro and in vivo functional activity of Chlamydia MurA, a UDP-N-acetylglucosamine enolpyruvyl transferase involved in peptidoglycan synthesis and fosfomycin resistance. J Bacteriol. 2003 Feb;185(4):1218-28. [PubMed:12562791]
  6. Brown ED, Vivas EI, Walsh CT, Kolter R: MurA (MurZ), the enzyme that catalyzes the first committed step in peptidoglycan biosynthesis, is essential in Escherichia coli. J Bacteriol. 1995 Jul;177(14):4194-7. [PubMed:7608103]
  7. Samland AK, Amrhein N, Macheroux P: Lysine 22 in UDP-N-acetylglucosamine enolpyruvyl transferase from Enterobacter cloacae is crucial for enzymatic activity and the formation of covalent adducts with the substrate phosphoenolpyruvate and the antibiotic fosfomycin. Biochemistry. 1999 Oct 5;38(40):13162-9. [PubMed:10529188]

Drug created on June 13, 2005 07:24 / Updated on January 14, 2018 10:04