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 8228

Conditions

Condition	Modality	Targets	Highest Phase	Product
Urinary tract infections 204 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	Curative		Approved 8360	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 1579 substrate 1709	substrate 1010	inhibitor 1837

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 901 CYP2C19 1463 CYP1A2 1509 CYP2A6 704 CYP2E1 876 OCT2 638	CYP1A2 1032 CYP2A6 523 CYP2B6 660 CYP2C8 688

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2C8 955	inhibitor 3240 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 639	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/19002438/	yes [IC50 1318 uM]
CYP1A2 1673	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition 250 uM]
CYP2C19 1537	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition 250 uM]
CYP2D6 1875	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition 250 uM]
CYP3A4 1909	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition 250 uM]
CYP2A6 736	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition <250 uM]
CYP2E1 964	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition <250 uM]

Drug as victim

Target	Modality	Activity
CYP1A2 1032	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes
CYP2A6 523	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes
CYP2B6 660	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes
CYP2C8 688	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes
CYP2C9 1010	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes
CYP3A4 1709	substrate 3326 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
Synthesis and biological evaluation of 5-arylfuro[2,3-d]pyrimidines as novel dihydrofolate reductase inhibitors.	1999 Feb	10071850
Identification of Cryptosporidium parvum dihydrofolate reductase inhibitors by complementation in Saccharomyces cerevisiae.	2000 Apr	10722506
Three-dimensional structure of M. tuberculosis dihydrofolate reductase reveals opportunities for the design of novel tuberculosis drugs.	2000 Jan 14	10623528
The pro-apoptotic Bcl-2 family member tBid localizes to mitochondrial contact sites.	2001	11716782
The VISA/GISA problem: therapeutic implications.	2001	11688538
[Whipple disease and non-Hodgkin lymphoma].	2001 Apr	11367979
HIV and drug allergy.	2001 Aug	11964706
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
Antimicrobial resistance of Shigella spp isolated from diarrheal patients between 1989 and 1998 in Vietnam.	2001 Dec	12041563
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
Travel-associated Burkholderia pseudomallei infection (Melioidosis) in a patient with cystic fibrosis: a case report.	2001 Jan	11112669
[Antimicrobial therapy of urinary tract infections].	2001 Jan-Feb	11379193
Infectious complications in chronic lymphoid malignancy.	2001 Jun	12057123
Antimicrobial sensitivity of Haemophilus influenzae isolates from bacterial conjunctivitis.	2001 Jun	11677911
Association between tuberculosis and HIV disease progression in a high tuberculosis prevalence area.	2001 Mar	11326821
Co-trimoxazole and genital ulceration.	2001 Mar	11321861
Changing pattern of biotypes, phage types & drug resistance of Salmonella typhi in Ludhiana during 1980-1999.	2001 May	11968951
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
Epidemiology of major respiratory pathogens.	2001 Nov	11936367
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
Use of systemic anti-infective agents in Iran during 1997-1998.	2001 Sep	11699624
Occurrence of enteric redmouth disease in rainbow trout (Oncorhynchus mykiss) on farms in Croatia.	2002	12237969
Burkholderia pseudomallei: abscess in an unusual site.	2002 Apr-Jun	12215696
Pneumocystis carinii: where are we now?	2002 Feb	11956498
A double-hand transplant can be worth the effort!	2002 Jul 15	12134104
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
Clinical signs and symptoms in the assessment of immunodeficiency in men with subtype C HIV infection in Harare, Zimbabwe.	2002 Mar-Apr	11976993
Urinary tract-derived Escherichia coli resistant to co-trimoxazole in Japan, where the drug is seldom used for treating acute urinary tract infections.	2002 May	12003990
Neutropenic enterocolitis (typhlitis) after pediatric bone marrow transplant.	2002 May	11987097

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 `Thu Jul 06 11:00:12 UTC 2023` Edited by `admin` on `Thu Jul 06 11:00:12 UTC 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