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

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
[A case report of urinary tract infection and meningitis caused by methicillin-resistant Staphylococcus aureus (MRSA) after transurethral resection of the prostate].	1999 Mar	10349306
Practice guidelines for the treatment of uncomplicated cystitis.	2001 Aug	12084260
Fosfomycin nebulizer therapy to chronic sinusitis.	2001 Aug	11489366
In vitro activity of fosfomycin in combination with various antistaphylococcal substances.	2001 Aug	11481290
Thermodynamic characterization of ligand-induced conformational changes in UDP-N-acetylglucosamine enolpyruvyl transferase.	2001 Aug 21	11502190
The effect of fosfomycin on glycopeptide antibiotic-induced nephrotoxicity in rats.	2001 Dec	11810591
[Correlation between sensitivity to fosfomycin and the presence of penicillinase PSE-1 in Pseudomonas aeruginosa].	2001 Feb	11265218
The effect of fosfomycin on neutrophil function.	2001 Feb	11157896
Evaluation of a new preservation solution containing fosfomycin for 20-hour canine lung preservation.	2001 Feb-Mar	11267112
[Drug resistance of Staphylococcus aureus strains, isolated from children with intestinal dysbacteriosis].	2001 Jan-Feb	11236517
[The epoxidation of cis-propenylphophonic acid to fosfomycin by Pencillium sp].	2001 Jun	12549091
[Effects of erythromycin and fosfomycin on Pseudomonas aeruginosa biofilm in vitro].	2001 Jun	11802985
Retrospective analysis of drug-induced urticaria and angioedema: a survey of 2287 patients.	2001 Nov	11792017
Transmissible fosfomycin resistance markers in urinary isolates and imported foodstuffs in the UK during 1994 and 1995.	2001 Nov	11679572
Biosynthetic pathway of insect juvenile hormone III in cell suspension cultures of the sedge Cyperus iria.	2001 Oct	11598232
[Multidrug-resistant and fluoroquinolone-resistant Salmonella enterica serotype Typhimurium definitive phage type 12 isolated from infantile diarrhea].	2001 Sep	11605192
Microbiological evaluation of a commercial transport system for urine samples.	2002	12387577
Mevalonate and nonmevalonate pathways for the biosynthesis of isoprene units.	2002 Aug	12353619
[Antibacterial activities of fosfomycin against several fresh clinical isolates--comparison of the test methods for antibacterial activity].	2002 Dec	12621737
E. coli MEP synthase: steady-state kinetic analysis and substrate binding.	2002 Jan 8	11772021
[Rational use of medications in the treatment of urinary infections].	2002 May 15	12031221
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
[Staphylococcus aureus meningitis with intermediate sensitivity to glycopeptides. Therapeutic indications].	2003 Feb 8	12610462
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.

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