TRIMETHOPRIM SULFATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	2C14H18N4O3.H2O4S
Molecular Weight	678.714
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OS(O)(=O)=O.COC1=CC(CC2=C(N)N=C(N)N=C2)=CC(OC)=C1OC.COC3=CC(CC4=C(N)N=C(N)N=C4)=CC(OC)=C3OC

InChI

InChIKey=UILMMYFRNCCPLK-UHFFFAOYSA-N

InChI=1S/2C14H18N4O3.H2O4S/c2*1-19-10-5-8(6-11(20-2)12(10)21-3)4-9-7-17-14(16)18-13(9)15;1-5(2,3)4/h2*5-7H,4H2,1-3H3,(H4,15,16,17,18);(H2,1,2,3,4)

HIDE SMILES / InChI

Molecular Formula	H2O4S
Molecular Weight	98.078
Charge	0
Count

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

Molecular Formula	C14H18N4O3
Molecular Weight	290.3177
Charge	0
Count

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

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf

Trimethoprim (TMP) is an antibiotic is used for the treatment of initial episodes of uncomplicated urinary tract infections due to susceptible strains of the following organisms: Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Enterobacter species, and coagulase-negative Staphylococcus species, including S. saprophyticus. Cultures and susceptibility tests should be performed to determine the susceptibility of the bacteria to trimethoprim. Therapy may be initiated prior to obtaining the results of these tests. Trimethoprim is rapidly absorbed following oral administration. It exists in the blood as unbound, protein-bound, and metabolized forms. Ten to twenty percent of trimethoprim is metabolized, primarily in the liver; the remainder is excreted unchanged in the urine. The principal metabolites of trimethoprim are the 1- and 3-oxides and the 3'- and 4'-hydroxy derivatives. The free form is considered to be the therapeutically active form. Approximately 44% of trimethoprim is bound to plasma proteins. Trimethoprim blocks the production of tetrahydrofolic acid from dihydrofolic acid by binding to and reversibly inhibiting the required enzyme, dihydrofolate reductase. This binding is very much stronger for the bacterial enzyme than for the corresponding mammalian enzyme

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Bacterial dihydrofolate reductase 5 Target ID: CHEMBL2364669 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19622858	Inhibitor 8146

Conditions

Condition	Modality	Targets	Highest Phase	Product
Urinary tract infections 202 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	Curative		Approved 8307	TRIMETHOPRIM Approved Use To reduce the development of drug-resistant bacteria and maintain the effectiveness of trimethoprim tablets, USP and other antibacterial drugs, trimethoprim tablets, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. For the treatment of initial episodes of uncomplicated urinary tract infections due to susceptible strains of the following organisms: Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Enterobacter species, and coagulase-negative Staphylococcus species, including S. saprophyticus. Cultures and susceptibility tests should be performed to determine the susceptibility of the bacteria to trimethoprim. Therapy may be initiated prior to obtaining the results of these tests. Launch Date 3.96748784E11

C_max

Value	Dose	Co-administered	Analyte	Population
2.1 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/5416179/	2 g single, oral dose: 2 g route of administration: Oral experiment type: SINGLE co-administered:		TRIMETHOPRIM plasma	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE food status: UNKNOWN
1 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	1 g single, oral dose: 1 g route of administration: Oral experiment type: SINGLE co-administered:		TRIMETHOPRIM plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
30.7 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/5416179/	2 g single, oral dose: 2 g route of administration: Oral experiment type: SINGLE co-administered:		TRIMETHOPRIM plasma	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
10 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	1 g single, oral dose: 1 g route of administration: Oral experiment type: SINGLE co-administered:		TRIMETHOPRIM plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
56% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	1 g single, oral dose: 1 g route of administration: Oral experiment type: SINGLE co-administered:		TRIMETHOPRIM plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
300 mg 2 times / day multiple, oral Highest studied dose Dose: 300 mg, 2 times / day Route: oral Route: multiple Dose: 300 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3890282	unhealthy Health Status: unhealthy Condition: severe shigellosis Sources: https://pubmed.ncbi.nlm.nih.gov/3890282	Sources: https://pubmed.ncbi.nlm.nih.gov/3890282
1 g 1 times / day multiple, oral Overdose Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	Other AEs: Nausea, Vomiting... Other AEs: Nausea Vomiting Dizziness Headaches Confusion Bone marrow depression Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf

AEs

AE	Dose	Population
Bone marrow depression	1 g 1 times / day multiple, oral Overdose Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf
Confusion	1 g 1 times / day multiple, oral Overdose Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf
Dizziness	1 g 1 times / day multiple, oral Overdose Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf
Headaches	1 g 1 times / day multiple, oral Overdose Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf
Nausea	1 g 1 times / day multiple, oral Overdose Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf
Vomiting	1 g 1 times / day multiple, oral Overdose Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1532 substrate 1670	substrate 985	inhibitor 1789

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 869 CYP2C19 1410 CYP1A2 1463 CYP2A6 670 CYP2E1 846 OCT2 630	CYP1A2 1013 CYP2A6 510 CYP2B6 648 CYP2C8 670

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2C8 923	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/\|https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1884466/ Page: 4.0	strong [IC50 32 uM]	yes (co-administration study) Comment: selective inhibition; Trimethoprim raised the AUC(0,∞) and Cmax of repaglinide by 61% (range, 30–117%; P = 0.0008) and 41% (P = 0.005), respectively; Although there was no detectable increase in the effect of repaglinide on blood glucose at the doses used, an enhanced risk of hypoglycaemia during concomitant use of trimethoprim and repaglinide is a possibility Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/\|https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1884466/ Page: 4.0
OCT2 631	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/19002438/	yes [IC50 1318 uM]
CYP1A2 1620	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition 250 uM]
CYP2C19 1484	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition 250 uM]
CYP2D6 1826	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition 250 uM]
CYP3A4 1857	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition 250 uM]
CYP2A6 702	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition <250 uM]
CYP2E1 929	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition <250 uM]

Drug as victim

Target	Modality	Activity
CYP1A2 1013	substrate 3264 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes
CYP2A6 510	substrate 3264 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes
CYP2B6 648	substrate 3264 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes
CYP2C8 670	substrate 3264 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes
CYP2C9 985	substrate 3264 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes
CYP3A4 1670	substrate 3264 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:45924	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:45924
ChemicalBook	CB2745185	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2745185
MolPort	MolPort-001-826-685	https://www.molport.com/shop/molecule-link/MolPort-001-826-685
Selleck Chemicals	trimethoprim	http://www.selleckchem.com/products/trimethoprim.html
ZINC	ZINC000006627681	http://zinc15.docking.org/substances/ZINC000006627681
eMolecules	27524526	https://www.emolecules.com/cgi-bin/more?vid=27524526
eMolecules	511466	https://www.emolecules.com/cgi-bin/more?vid=511466

PubMed

Title	Date	PubMed
The pro-apoptotic Bcl-2 family member tBid localizes to mitochondrial contact sites.	2001	11716782
Clinical significance and impact on mortality of extended-spectrum beta lactamase-producing Enterobacteriaceae isolates in nosocomial bacteremia.	2001	11303808
A report case of Cyclospora and Cryptosporidium mixed infection in a HIV-negative child in Thailand.	2001 Apr	11460975
[Whipple disease and non-Hodgkin lymphoma].	2001 Apr	11367979
Aminopyrimidine-carboxyl(ate) interactions in trimethoprim maleate, an antifolate drug.	2001 Apr	11313594
To test or not to test--ethical dilemmas and practical realities in the use of co-trimoxazole and nevirapine in HIV-infected adults.	2001 Aug	11584779
Predominance of a methicillin-resistant Staphylococcus aureus clone susceptible to erythromycin and several other non-beta-lactam antibiotics in a Greek hospital.	2001 Aug	11481293
Effects of trimethoprim and co-trimoxazole on the morphology of Listeria monocytogenes in culture medium and after phagocytosis.	2001 Aug	11481287
Antimicrobial resistance of Shigella spp isolated from diarrheal patients between 1989 and 1998 in Vietnam.	2001 Dec	12041563
Rapid detection of Haemophilus influenzae type b in Bangladeshi children with pneumonia and meningitis by PCR and analysis of antimicrobial resistance.	2001 Dec	11855348
Pneumocystis carinii pneumonitis in haemophagocytic lymphohistiocytosis.	2001 Dec	11853350
Antibiotic failure in the treatment of urinary tract infections in young women.	2001 Dec	11733475
Neonatal brucellosis and blood transfusion: case report and review of the literature.	2001 Dec	11732154
Prevalence of antimicrobial resistance in Streptococcus pneumoniae circulating in Italy: results of the Italian Epidemiological Observatory Survey (1997-1999).	2001 Fall	11759090
Co-trimoxazole resistant Brucella.	2001 Feb	11245355
Bsoft: image and molecular processing in electron microscopy.	2001 Feb-Mar	11472087
Antistaphylococcal (MSSA, MRSA, MSSE, MRSE) antibiotics.	2001 Jan	11190346
[Antimicrobial therapy of urinary tract infections].	2001 Jan-Feb	11379193
Pulmonary nocardiosis in human immunodeficiency virus infection: a tuberculosis mimic.	2001 Jan-Mar	11590288
Epidemic of Vibrio cholerae serogroup O139 in Berhampur, Orissa.	2001 Jul	11762200
Brucellosis in children of Dhofar Region, Oman.	2001 Jul	11479644
Etiologies of the urinary tract infections in a Yemeni City.	2001 Jul	11479641
Pneumocystis carinii pneumonia in patients being registered for smear-negative pulmonary tuberculosis in Malawi.	2001 Jul-Aug	11579884
Successful therapy combined with surgery for severe post-transplant nocardiosis.	2001 Jul-Aug	11506255
Bacteriuria in the elderly population in a developing country.	2001 Jul-Aug	11491272
Infectious complications in chronic lymphoid malignancy.	2001 Jun	12057123
Successful management of Brucella mellitensis endocarditis with combined medical and surgical approach.	2001 Jun	11404134
Association between tuberculosis and HIV disease progression in a high tuberculosis prevalence area.	2001 Mar	11326821
Co-trimoxazole and genital ulceration.	2001 Mar	11321861
Patterns of antibiotic resistance, serotype distribution, and patient demographics of Streptococcus pneumoniae in Hong Kong.	2001 Mar-Apr	11173812
Effect of early chemoprophylaxis with co-trimoxazole on nutritional status evolution in HIV-1-infected adults in Abidjan, Côte d'Ivoire.	2001 May 4	11399959
A common-source water-borne outbreak of multidrug-resistant typhoid fever in a rural Thai community.	2001 Nov	11853291
Synthesis of 2,4-diamino-6-(thioarylmethyl)pyrido[2,3-d]pyrimidines as dihydrofolate reductase inhibitors.	2001 Nov	11597474
Co-trimoxazole compared with sulfadoxine-pyrimethamine in the treatment of uncomplicated malaria in Kenyan children.	2001 Nov-Dec	11816440
Bacterial aetiology and anti-microbial resistance of childhood diarrhoea in Yemen.	2001 Oct	11695731
Antibiotic use and resistance of Streptococcus pneumoniae in The Netherlands during the period 1994-1999.	2001 Sep	11533014
In vitro activity of novel fluoroquinolones against Streptococcus pneumoniae isolated from children with acute otitis media.	2001 Sep-Oct	11561138
Developing and testing instruments to measure client outcomes at the Comox Valley Nursing Center.	2001 Sep-Oct	11559416
Occurrence of enteric redmouth disease in rainbow trout (Oncorhynchus mykiss) on farms in Croatia.	2002	12237969
[Antibiotic resistance of staphylococci isolated from outpatients].	2002	12185699
Incidence and molecular analysis of Vibrio cholerae associated with cholera outbreak subsequent to the super cyclone in Orissa, India.	2002 Apr	12002529
[General antibiotic therapy in acne].	2002 Apr 15	12053791
Burkholderia pseudomallei: abscess in an unusual site.	2002 Apr-Jun	12215696
Shigellosis linked to sex venues, Australia.	2002 Aug	12141976
Allergic adverse reactions to sulfonamides.	2002 Jan	11895621
Facilitating changes in perinatal smoking. The impact of a stage-based workshop for care-providers in British Columbia.	2002 Jul-Aug	12154532
Rapid increase in macrolide resistance among penicillin non-susceptible pneumococci in Finland, 1996-2000.	2002 May	12003972
Emergence of vancomycin-intermediate Staphylococcus aureus and S. sciuri, Greece.	2002 May	11996696
Neutropenic enterocolitis (typhlitis) after pediatric bone marrow transplant.	2002 May	11987097
First characterization of a cluster of VanA-type glycopeptide-resistant Enterococcus faecium, Colombia.	2002 Sep	12194774

Patents

Sample Use Guides

In Vivo Use Guide

The usual oral adult dosage is 100 mg of trimethoprim every 12 hours or 200 mg of trimethoprim every 24 hours, each for 10 days. The use of trimethoprim in patients with a creatinine clearance of less than 15 mL/min is not recommended. For patients with a creatinine clearance of 15 to 30 mL/min, the dose should be 50 mg every 12 hours.

Route of Administration: Oral

In Vitro Use Guide

In vitro susceptibility of bacterial isolates to sulfamethoxazole, trimethoprim and trimethoprim/sulfamethoxazole was determined using disk diffusion. E. coli susceptibility to trimethoprim was 70%, comparable to the 70% of trimethoprim/sulfamethoxazole (p = 0.9)and higher than the 56.9% of sulfamethoxazole (p <0.05).

Substance Class	Chemical Created by `admin` on `Fri Dec 16 16:55:52 UTC 2022` Edited by `admin` on `Fri Dec 16 16:55:52 UTC 2022`
Record UNII	E377MF8EQ8
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TRIMETHOPRIM SULFATE

Official Name

English

TRIMETHOPRIM SULFATE [USP MONOGRAPH]

Common Name

English

TRIMETHOPRIM SULFATE [USAN]

Common Name

English

POLYTRIM COMPONENT TRIMETHOPRIM SULFATE

Common Name

English

TRIMETHOPRIM SULPHATE

Common Name

English

BW-72U

Code

English

TRIMETHOPRIM SULFATE [ORANGE BOOK]

Common Name

English

TRIMETHOPRIM SULFATE [VANDF]

Common Name

English

Trimethoprim sulfate [WHO-DD]

Common Name

English

BW 72U

Code

English

TRIMETHOPRIM SULFATE [MART.]

Common Name

English

TRIMETHOPRIM SULFATE COMPONENT OF POLYTRIM

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C255