TRIMETHOPRIM

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H18N4O3
Molecular Weight	290.3177
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC(CC2=C(N)N=C(N)N=C2)=CC(OC)=C1OC

InChI

InChIKey=IEDVJHCEMCRBQM-UHFFFAOYSA-N

InChI=1S/C14H18N4O3/c1-19-10-5-8(6-11(20-2)12(10)21-3)4-9-7-17-14(16)18-13(9)15/h5-7H,4H2,1-3H3,(H4,15,16,17,18)

HIDE SMILES / InChI

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 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Urinary tract infections 205 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	Curative		Approved 8429	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 1982

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 1587 substrate 1737	substrate 1037	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 911 CYP2C19 1478 CYP1A2 1524 CYP2A6 707 CYP2E1 882 OCT2 647	CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2C8 693

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2C8 965	inhibitor 3277 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 648	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19002438/	yes [IC50 1318 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition 250 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition 250 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition 250 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition 250 uM]
CYP2A6 739	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition <250 uM]
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition <250 uM]

Drug as victim

Target	Modality	Activity
CYP1A2 1054	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes
CYP2A6 543	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes
CYP2B6 664	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes
CYP2C8 693	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes
CYP2C9 1037	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes
CYP3A4 1737	substrate 3367 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
The VISA/GISA problem: therapeutic implications.	2001	11688538
HIV and drug allergy.	2001 Aug	11964706
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
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
Empirical treatment of uncomplicated urinary tract infection by community pharmacist in the Eastern province of Saudi Arabia.	2001 Dec	11802186
Gradient diffusion antibiotic susceptibility testing of potentially probiotic lactobacilli.	2001 Dec	11770631
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
Epidemic of Vibrio cholerae serogroup O139 in Berhampur, Orissa.	2001 Jul	11762200
Antimicrobial sensitivity of Haemophilus influenzae isolates from bacterial conjunctivitis.	2001 Jun	11677911
Changing pattern of biotypes, phage types & drug resistance of Salmonella typhi in Ludhiana during 1980-1999.	2001 May	11968951
Epidemiology of major respiratory pathogens.	2001 Nov	11936367
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
Epidemiological analysis of Salmonella enteritidis isolates in Singapore.	2001 Oct	11798253
Susceptibility patterns and serotypes of non-typhoidal salmonella in Trinidad.	2001 Oct	11744940
Bacterial aetiology and anti-microbial resistance of childhood diarrhoea in Yemen.	2001 Oct	11695731
Epidemiology of shigellosis in Lagos, Nigeria: trends in antimicrobial resistance.	2001 Sep	11761772
Use of systemic anti-infective agents in Iran during 1997-1998.	2001 Sep	11699624
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
Staphylococcus aureus and Wegener's granulomatosis.	2002	11879541
Trimethoprim-induced aseptic meningitis in an adolescent male.	2002 Aug	12165625
Shigellosis linked to sex venues, Australia.	2002 Aug	12141976
Pneumocystis carinii: where are we now?	2002 Feb	11956498
Clinical efficacy of co-trimoxazole versus amoxicillin twice daily for treatment of pneumonia: a randomised controlled clinical trial in Pakistan.	2002 Feb	11827905
Prophylactic antibiotic use in transurethral prostatic resection: a meta-analysis.	2002 Feb	11792921
Clinical and biological evolution of HIV-1 seroconverters in Abidjan, Côte d'Ivoire, 1997-2000.	2002 Feb 1	11832684
Allergic adverse reactions to sulfonamides.	2002 Jan	11895621
Inhibition of Pneumocystis carinii, Toxoplasma gondii, and Mycobacterium avium dihydrofolate reductases by 2,4-diamino-5-[2-methoxy-5-(omega-carboxyalkyloxy)benzyl]pyrimidines: marked improvement in potency relative to trimethoprim and species selectivity relative to piritrexim.	2002 Jan 3	11754594
A double-hand transplant can be worth the effort!	2002 Jul 15	12134104
Facilitating changes in perinatal smoking. The impact of a stage-based workshop for care-providers in British Columbia.	2002 Jul-Aug	12154532
Prevalence of and resistance to anti-microbial drugs in selected microbial species isolated from bulk milk samples.	2002 Jun	12121041
In vitro activities of pentamidine, pyrimethamine, trimethoprim, and sulfonamides against Aspergillus species.	2002 Jun	12019133
HIV-1/AIDS and maternal and child health in Africa.	2002 Jun 15	12086778
A disseminated multidrug-resistant clonal group of uropathogenic Escherichia coli in pyelonephritis.	2002 Jun 29	12103291
Modified antimicrobial disc susceptibility testing for nutritionally-variant streptococci.	2002 Mar	12118443
The relation between sale of antimicrobial drugs and antibiotic resistance in uropathogens in general practice.	2002 Mar	12086284
A European study on the relationship between antimicrobial use and antimicrobial resistance.	2002 Mar	11927025
Q fever during pregnancy: diagnosis, treatment, and follow-up.	2002 Mar 25	11911725
Changes in Escherichia coli resistance to co-trimoxazole in tuberculosis patients and in relation to co-trimoxazole prophylaxis in Thyolo, Malawi.	2002 Mar-Apr	12055816
A simple clinical and paraclinical score predictive of CD4 cells counts below 400/mm3 in HIV-infected adults in Dakar University Hospital, Senegal.	2002 Mar-Apr	12055807
Clinical signs and symptoms in the assessment of immunodeficiency in men with subtype C HIV infection in Harare, Zimbabwe.	2002 Mar-Apr	11976993
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 `Sat Dec 16 05:13:50 GMT 2023` Edited by `admin` on `Sat Dec 16 05:13:50 GMT 2023`
Record UNII	AN164J8Y0X
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TRIMETHOPRIM

Official Name

English

TRIMETHOPRIM COMPONENT OF SULFAMETHOPRIM

Common Name

English

TRIMETHOPRIM COMPONENT OF BACTRIM

Common Name

English

NIH-204

Code

English

SULMEPRIM COMPONENT TRIMETHOPRIM

Common Name

English

BACTRIM DS COMPONENT TRIMETHOPRIM

Common Name

English

trimethoprim [INN]

Common Name

English

2,4-PYRIMIDINEDIAMINE, 5-((3,4,5-TRIMETHOXYPHENYL)METHYL)-

Systematic Name

English

NSC-106568

Code

English

BACTRIM PEDIATRIC COMPONENT TRIMETHOPRIM

Common Name

English

SEPTRA COMPONENT TRIMETHOPRIM

Common Name

English

TRIMETHOPRIM COMPONENT OF SEPTRA

Common Name

English

WELLCOPRIM

Common Name

English

Co-trimoxazole component trimethoprim

Common Name

English

TRIMETHOPRIM [HSDB]

Common Name

English

TRIMETHOPRIM COMPONENT OF COTRIM

Common Name

English

TRIMETHOPRIM COMPONENT OF UROPLUS

Common Name

English

COTRIM D.S. COMPONENT TRIMETHOPRIM

Common Name

English

TRIMETHOPRIM COMPONENT OF COTRIM D.S.

Common Name

English

TRIMETHOPRIM COMPONENT OF BACTRIM PEDIATRIC

Common Name

English

TRIMETHOPRIM [VANDF]

Common Name

English

TRIMETHOPRIM [USAN]

Common Name

English

BW-56-72

Code

English

TRIMETHOPRIMUM [WHO-IP LATIN]

Common Name

English

TRIMETHOPRIM [USP MONOGRAPH]

Common Name

English

SULFATRIM COMPONENT TRIMETHOPRIM

Common Name

English

TRIMETHOPRIM [JAN]

Common Name

English

SULFAMETHOPRIM COMPONENT TRIMETHOPRIM

Common Name

English

TRIMETHOPRIM COMPONENT OF SULFATRIM

Common Name

English

TRIMPEX

Brand Name

English

TRIMETHOPRIM [ORANGE BOOK]

Common Name

English

PROLOPRIM

Brand Name

English

TRIMETHOPRIM [MART.]

Common Name

English

TMP

Common Name

English

TRIMETHOPRIM [EP IMPURITY]

Common Name

English

Trimethoprim [WHO-DD]

Common Name

English

TRIMETHOPRIM [GREEN BOOK]

Common Name

English

BACTRIM COMPONENT TRIMETHOPRIM

Common Name

English

TRIMETHOPRIM COMPONENT OF SULMEPRIM

Common Name

English

TRIMETHOPRIM [MI]

Common Name

English

COTRIM COMPONENT TRIMETHOPRIM

Common Name

English

BW 56-72

Code

English

TRIMETHOPRIM COMPONENT OF BACTRIM DS

Common Name

English

TRIMETHOPRIM [USP-RS]

Common Name

English

INFECTOTRIMET

Common Name

English

UROPLUS COMPONENT TRIMETHOPRIM

Common Name

English

2,4-Diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine

Systematic Name

English

TRIMETHOPRIM [EP MONOGRAPH]

Common Name

English

Classification Tree Code System Code

WHO-ATC

J01EE07