FOSFOMYCIN TROMETHAMINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C4H11NO3.C3H7O4P
Molecular Weight	259.1941
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@@H]1O[C@@H]1P(O)(O)=O.NC(CO)(CO)CO

InChI

InChIKey=QZJIMDIBFFHQDW-LMLSDSMGSA-N

InChI=1S/C4H11NO3.C3H7O4P/c5-4(1-6,2-7)3-8;1-2-3(7-2)8(4,5)6/h6-8H,1-3,5H2;2-3H,1H3,(H2,4,5,6)/t;2-,3+/m.0/s1

HIDE SMILES / InChI

Molecular Formula	C4H11NO3
Molecular Weight	121.135
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C3H7O4P
Molecular Weight	138.059
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/050717s007lbl.pdf | https://www.drugbank.ca/drugs/DB00828 | http://www.msdmanuals.com/professional/infectious-diseases/bacteria-and-antibacterial-drugs/fosfomycin

Fosfomycin (marketed under the trade names Monurol and Monuril) is a broad-spectrum antibiotic. Monurol (fosfomycin tromethamine) sachet contains fosfomycin tromethamine, a synthetic, broad spectrum, bactericidal antibiotic for oral administration. Monurol is indicated only for the treatment of uncomplicated urinary tract infections (acute cystitis) in women due to susceptible strains of Escherichia coli and Enterococcus faecalis. 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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
UDP-N-acetylglucosamine 1-carboxyvinyltransferase 9 Target ID: CHEMBL1984 Sources: https://www.drugbank.ca/drugs/DB00828 \| https://www.ncbi.nlm.nih.gov/pubmed/20392080 \| https://www.ncbi.nlm.nih.gov/pubmed/22378791	Inhibitor 8297		100.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Acute cystitis 8 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/50717SLR004_Monurol_lbl.pdf	Curative		Approved 8429	MONUROL Approved Use MONUROL is indicated only for the treatment of uncomplicated urinary tract infections (acute cystitis) in women due to susceptible strains of Escherichia coli and Enterococcus faecalis. MONUROL is not indicated for the treatment of pyelonephritis or perinephric abscess. If persistence or reappearance of bacteriuria occurs after treatment with MONUROL, other therapeutic agents should be selected. Launch Date 8.5095357E11

C_max

Value	Dose	Co-administered	Analyte	Population
26.8 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28630194	3 g single, oral dose: 3 g route of administration: Oral experiment type: SINGLE co-administered:		FOSFOMYCIN TROMETHAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
191 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28630194	3 g single, oral dose: 3 g route of administration: Oral experiment type: SINGLE co-administered:		FOSFOMYCIN TROMETHAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
9.04 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28630194	3 g single, oral dose: 3 g route of administration: Oral experiment type: SINGLE co-administered:		FOSFOMYCIN TROMETHAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
100% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/050717s009lbl.pdf	unknown, unknown		FOSFOMYCIN TROMETHAMINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
3 g 1 times / day single, oral Recommended Dose: 3 g, 1 times / day Route: oral Route: single Dose: 3 g, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/050717Orig1s000rev.pdf Page: MON-US-02	unhealthy, 32 n = 426 Health Status: unhealthy Condition: Infection Age Group: 32 Sex: M+F Population Size: 426 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/050717Orig1s000rev.pdf Page: MON-US-02	Disc. AE: Diarrhea, Erythema... AEs leading to discontinuation/dose reduction: Diarrhea Erythema Vomiting Rash Dry mouth Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/050717Orig1s000rev.pdf Page: MON-US-02

AEs

AE	Significance	Dose	Population
Diarrhea	Disc. AE	3 g 1 times / day single, oral Recommended Dose: 3 g, 1 times / day Route: oral Route: single Dose: 3 g, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/050717Orig1s000rev.pdf Page: MON-US-02	unhealthy, 32 n = 426 Health Status: unhealthy Condition: Infection Age Group: 32 Sex: M+F Population Size: 426 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/050717Orig1s000rev.pdf Page: MON-US-02
Dry mouth	Disc. AE	3 g 1 times / day single, oral Recommended Dose: 3 g, 1 times / day Route: oral Route: single Dose: 3 g, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/050717Orig1s000rev.pdf Page: MON-US-02	unhealthy, 32 n = 426 Health Status: unhealthy Condition: Infection Age Group: 32 Sex: M+F Population Size: 426 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/050717Orig1s000rev.pdf Page: MON-US-02
Erythema	Disc. AE	3 g 1 times / day single, oral Recommended Dose: 3 g, 1 times / day Route: oral Route: single Dose: 3 g, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/050717Orig1s000rev.pdf Page: MON-US-02	unhealthy, 32 n = 426 Health Status: unhealthy Condition: Infection Age Group: 32 Sex: M+F Population Size: 426 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/050717Orig1s000rev.pdf Page: MON-US-02
Rash	Disc. AE	3 g 1 times / day single, oral Recommended Dose: 3 g, 1 times / day Route: oral Route: single Dose: 3 g, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/050717Orig1s000rev.pdf Page: MON-US-02	unhealthy, 32 n = 426 Health Status: unhealthy Condition: Infection Age Group: 32 Sex: M+F Population Size: 426 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/050717Orig1s000rev.pdf Page: MON-US-02
Vomiting	Disc. AE	3 g 1 times / day single, oral Recommended Dose: 3 g, 1 times / day Route: oral Route: single Dose: 3 g, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/050717Orig1s000rev.pdf Page: MON-US-02	unhealthy, 32 n = 426 Health Status: unhealthy Condition: Infection Age Group: 32 Sex: M+F Population Size: 426 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/050717Orig1s000rev.pdf Page: MON-US-02

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP 111	CYP 270 UGT 192

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 147	inhibitor 3277 Sources: https://www.tga.gov.au/sites/default/files/auspar-fosfomycin-trometamol-180907.pdf#page=74 Page: 74.0	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 270	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21914036/ Page: -	no
UGT 192	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21914036/ Page: -	no

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:28915	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:28915
ZINC	ZINC000001530427	http://zinc15.docking.org/substances/ZINC000001530427

PubMed

Title	Date	PubMed
Practice guidelines for the treatment of uncomplicated cystitis.	2001 Aug	12084260
[Fosfomycin: an underrated antibiotic for urinary tract infections due to Escherichia coli].	2001 Dec	11844449
[The epoxidation of cis-propenylphophonic acid to fosfomycin by Pencillium sp].	2001 Jun	12549091
Microbiological evaluation of a commercial transport system for urine samples.	2002	12387577
Therapy of uncomplicated urinary tract infections.	2002	12140716
In vitro susceptibility of vancomycin-resistant enterococci (VRE) to fosfomycin.	2002 Apr	12007445
Mevalonate and nonmevalonate pathways for the biosynthesis of isoprene units.	2002 Aug	12353619
Efficacy of calcium fosfomycin for the treatment of experimental infections of broiler chickens with Escherichia coli O78:K80.	2002 Aug	12241095
Comparative pulsed-field gel electrophoresis typing of gentamicin-resistant and -susceptible methicillin-resistant Staphylococcus aureus strains isolated in France between 1991 and 1998. Changes in antibiotic susceptibility.	2002 Aug	12183140
[Antibacterial activities of fosfomycin against several fresh clinical isolates--comparison of the test methods for antibacterial activity].	2002 Dec	12621737
Biofilm testing of Staphylococcus epidermidis clinical isolates: low performance of vancomycin in relation to other antibiotics.	2002 Dec	12543535
[Rhône-Alpes observatory of Streptococcus pneumoniae in 1999: 35 cases of meningitis].	2002 Dec	12504368
Time- and dose-dependent effect of fosfomycin on suppression of infection-induced endotoxin shock in mice.	2002 Dec	12499661
Fosmidomycin for malaria.	2002 Dec 14	12493263
Mechanistic studies of HPP epoxidase: configuration of the substrate governs its enzymatic fate.	2002 Dec 2	12458528
Time-dependent toxicity in the long-term inhibition assay with Vibrio fischeri.	2002 Feb	11999781
Antibiotics as anti-inflammatory agents.	2002 Jan	12054075
Pseudo-septic meningeal reaction after intradural glucocorticoid therapy for sciatica.	2002 Jan	11858368
Urinary tract infection: traditional pharmacologic therapies.	2002 Jul 8	12113870
In-vitro susceptibility of quinolone-resistant clinical isolates of Escherichia coli to fosfomycin trometamol.	2002 Jun	12120876
[Treatment in initial stage of VTEC infection].	2002 Jun	12078083
[Indicators for early diagnosis of enterohemorrhagic Escherichia coli infection and methods for final diagnosis].	2002 Jun	12078081
Antisense and chemical suppression of the nonmevalonate pathway affects ent-kaurene biosynthesis in Arabidopsis.	2002 Jun	12029484
A pathway-specific cell based screening system to detect bacterial cell wall inhibitors.	2002 Mar	12014443
Fosfomycin inhibits neutrophil function via a protein kinase C-dependent signaling pathway.	2002 Mar	11962730
Effectiveness of fosfomycin combined with other antimicrobial agents against multidrug-resistant Pseudomonas aeruginosa isolates using the efficacy time index assay.	2002 Mar	11957118
EPR study of substrate binding to the Mn(II) active site of the bacterial antibiotic resistance enzyme FosA: a better way to examine Mn(II).	2002 Mar 13	11878987
In vitro susceptibility of four serotypes of enterohaemorrhagic Escherichia coli to antimicrobial agents.	2002 May	12033514
Emergence of vancomycin-intermediate Staphylococcus aureus and S. sciuri, Greece.	2002 May	11996696
[Rational use of medications in the treatment of urinary infections].	2002 May 15	12031221
Flow injection spectrophotometric determination of the antibiotic fosfomycin in pharmaceutical products and urine samples after on-line thermal-induced digestion.	2002 May 15	12009702
Susceptibility of Streptococcus mutans and Streptococcus sobrinus to cell wall inhibitors and development of a novel selective medium for S. sobrinus.	2002 May-Jun	12065966
Penetration of fosfomycin into the parenchyma of human brain: a case study in three patients.	2002 Nov	12445038
Elucidation of the methylerythritol phosphate pathway for isoprenoid biosynthesis in bacteria and plastids. A metabolic milestone achieved through genomics.	2002 Nov	12427975
Natural antibiotic susceptibility of Enterobacter spp., with special reference to Enterobacter aerogenes and Enterobacter intermedius strains.	2002 Oct	12462424
Empirical treatment of adult postsurgical nosocomial meningitis.	2002 Oct	12382127
On-line analysis of the (13)CO(2) labeling of leaf isoprene suggests multiple subcellular origins of isoprene precursors.	2002 Oct	12355149
Natural antibiotic susceptibility of Enterobacter amnigenus, Enterobacter cancerogenus, Enterobacter gergoviae and Enterobacter sakazakii strains.	2002 Sep	12427217
Role of fosfomycin in a synergistic combination with ofloxacin against Pseudomonas aeruginosa growing in a biofilm.	2002 Sep	12373484
Crystal structure of a genomically encoded fosfomycin resistance protein (FosA) at 1.19 A resolution by MAD phasing off the L-III edge of Tl(+).	2002 Sep 18	12224946
On the transformation of (S)-2-hydroxypropylphosphonic acid into fosfomycin in Streptomyces fradiae--a unique method of epoxide ring formation.	2002 Sep 2	12210983
Life-threatening infantile diarrhea from fluoroquinolone-resistant Salmonella enterica typhimurium with mutations in both gyrA and parC.	2003 Feb	12604000
Urinary tract infection: traditional pharmacologic therapies.	2003 Feb	12601341
[Staphylococcus aureus meningitis with intermediate sensitivity to glycopeptides. Therapeutic indications].	2003 Feb 8	12610462
Moellerella wisconsensis: identification, natural antibiotic susceptibility and its dependency on the medium applied.	2003 Jan	12573545
An international survey of the antimicrobial susceptibility of pathogens from uncomplicated urinary tract infections: the ECO.SENS Project.	2003 Jan	12493789
Structure and function of the Mur enzymes: development of novel inhibitors.	2003 Jan	12492849
Identification and disruption of btlA, a locus involved in bile tolerance and general stress resistance in Listeria monocytogenes.	2003 Jan 21	12583894
Inhibition of paclitaxel and baccatin III accumulation by mevinolin and fosmidomycin in suspension cultures of Taxus baccata.	2003 Mar 6	12568744
Structural basis of fosmidomycin action revealed by the complex with 2-C-methyl-D-erythritol 4-phosphate synthase (IspC). Implications for the catalytic mechanism and anti-malaria drug development.	2003 May 16	12621040

Patents

Sample Use Guides

In Vivo Use Guide

Urinary tract infections, uncomplicated: Oral: Females: Single dose of 3 g in 3 to 4 oz (90 to 120 mL) of water Complicated UTI (off-label): Males: Oral: 3 g every 2 to 3 days for 3 doses

Route of Administration: Oral

In Vitro Use Guide

Fosfomycin MIC50 and MIC90 values were 16 and 128 ug/mL for the 38 ceftazidime-nonsusceptible Enterobacter isolates and 64 and 128 ug/mL for the 15 ceftazidime-nonsusceptible P. aeruginosa isolates, respectively.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:30:30 UTC 2023` Edited by `admin` on `Fri Dec 15 15:30:30 UTC 2023`
Record UNII	7FXW6U30GY
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

FOSFOMYCIN TROMETHAMINE

Official Name

English

FOSFOMYCIN TROMETHAMINE [VANDF]

Common Name

English

FOSFOMYCIN TROMETAMOL

Common Name

English

PHOSPHONIC ACID, (3-METHYLOXIRANYL)-, (2R-CIS)-, COMPD. WITH 2-AMINO-2-(HYDROXYMETHYL)-1,3-PROPANEDIOL (1:1)

Common Name

English

FOSFOMYCIN TROMETAMOL (1:1)

Common Name

English

Fosfomycin trometamol [WHO-DD]

Common Name

English

Z-1282

Code

English

FOSFOMYCIN TROMETHAMINE [MI]

Common Name

English

FOSFOMYCIN TROMETAMOL [EP MONOGRAPH]

Common Name

English

(1R,2S)-(1,2-Epoxypropyl)phosphonic acid, compound with 2-amino-2-(hydroxymethyl)-1,3-propanediol (1:1)

Common Name

English

FOSFOMYCIN TROMETAMOL SALT

Common Name

English

FOSFOMYCIN TROMETHAMINE [USP MONOGRAPH]

Common Name

English

FOSFOMYCIN TROMETHAMINE [USP-RS]

Common Name

English

Z 1282

Code

English

FOSFOMYCIN TROMETHAMINE [USAN]

Common Name

English

FOSFOMYCIN TROMETHAMINE [ORANGE BOOK]

Common Name

English

FOSFOMYCIN TROMETAMOL [MART.]

Common Name

English

MONUROL

Brand Name

English

Classification Tree Code System Code

NCI_THESAURUS

C255