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 1996

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
Thermodynamic characterization of ligand-induced conformational changes in UDP-N-acetylglucosamine enolpyruvyl transferase.	2001 Aug 21	11502190
[Fosfomycin: an underrated antibiotic for urinary tract infections due to Escherichia coli].	2001 Dec	11844449
Isoprene produced by leaves protects the photosynthetic apparatus against ozone damage, quenches ozone products, and reduces lipid peroxidation of cellular membranes.	2001 Dec	11743121
[Antibiotic resistance of Staphylococcus aureus in urban experience: 6 month study in Aquitaine].	2001 Feb	11265221
Two cases of severe bronchopneumonia due to influenza A (H3N2) virus: detection of influenza virus gene using reverse transcription polymerase chain reaction.	2001 Jan	11201374
[Effects of erythromycin and fosfomycin on Pseudomonas aeruginosa biofilm in vitro].	2001 Jun	11802985
[Pattern of antimicrobial susceptibility in uropathogen isolates from children].	2001 Mar	11376352
Protein purification and function assignment of the epoxidase catalyzing the formation of fosfomycin.	2001 May 16	11457256
Retrospective analysis of drug-induced urticaria and angioedema: a survey of 2287 patients.	2001 Nov	11792017
Sharpless asymmetric dihydroxylation of trans-propenylphosphonate by using a modified AD-mix-alpha and the synthesis of fosfomycin.	2001 Nov 16	11701057
Time-kill evaluation of antimicrobial regimens against clinical isolates of penicillin-resistant Streptococcus pneumoniae.	2001 Oct	11760218
In vitro susceptibility of vancomycin-resistant enterococci (VRE) to fosfomycin.	2002 Apr	12007445
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
In vitro activity of the aerosolized agents colistin and tobramycin and five intravenous agents against Pseudomonas aeruginosa isolated from cystic fibrosis patients in southwestern Germany.	2002 Feb	11815589
Natural antibiotic susceptibility and biochemical profiles of Yersinia enterocolitica-like strains: Y. bercovieri, Y. mollaretii, Y. aldovae and 'Y. ruckeri'.	2002 Jan	11800473
E. coli MEP synthase: steady-state kinetic analysis and substrate binding.	2002 Jan 8	11772021
[Indicators for early diagnosis of enterohemorrhagic Escherichia coli infection and methods for final diagnosis].	2002 Jun	12078081
Effectiveness of fosfomycin combined with other antimicrobial agents against multidrug-resistant Pseudomonas aeruginosa isolates using the efficacy time index assay.	2002 Mar	11957118
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
Natural antibiotic susceptibility of Enterobacter spp., with special reference to Enterobacter aerogenes and Enterobacter intermedius strains.	2002 Oct	12462424
Natural antibiotic susceptibility of Enterobacter amnigenus, Enterobacter cancerogenus, Enterobacter gergoviae and Enterobacter sakazakii strains.	2002 Sep	12427217
Identification and disruption of btlA, a locus involved in bile tolerance and general stress resistance in Listeria monocytogenes.	2003 Jan 21	12583894

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 GMT 2023` Edited by `admin` on `Fri Dec 15 15:30:30 GMT 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