U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula 2C14H18N4O3.H2O4S
Molecular Weight 678.7161
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TRIMETHOPRIM SULFATE

SMILES

COc1cc(Cc2c[nH]c(=N)[nH]c2=N)cc(c1OC)OC.COc1cc(Cc2c[nH]c(=N)[nH]c2=N)cc(c1OC)OC.OS(=O)(=O)O

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 98.0796
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C14H18N4O3
Molecular Weight 290.3183
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
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
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2.1 μg/mL
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
30.7 μg × h/mL
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
10 h
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
56%
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

Doses

DosePopulationAdverse 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:
unhealthy
Health Status: unhealthy
Condition: severe shigellosis
Sources:
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:
unhealthy
Other AEs: Nausea, Vomiting...
Other AEs:
Nausea
Vomiting
Dizziness
Headaches
Confusion
Bone marrow depression
Sources:
AEs

AEs

AESignificanceDosePopulation
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:
unhealthy
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:
unhealthy
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:
unhealthy
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:
unhealthy
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:
unhealthy
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:
unhealthy
Overview

Overview

OverviewOther

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
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
Page: 4.0
yes [IC50 1318 uM]
yes [Inhibition 250 uM]
yes [Inhibition 250 uM]
yes [Inhibition 250 uM]
yes [Inhibition 250 uM]
yes [Inhibition <250 uM]
yes [Inhibition <250 uM]
Drug as victim
PubMed

PubMed

TitleDatePubMed
The pro-apoptotic Bcl-2 family member tBid localizes to mitochondrial contact sites.
2001
The VISA/GISA problem: therapeutic implications.
2001
HIV and drug allergy.
2001 Aug
Antimicrobial resistance of Shigella spp isolated from diarrheal patients between 1989 and 1998 in Vietnam.
2001 Dec
Rapid detection of Haemophilus influenzae type b in Bangladeshi children with pneumonia and meningitis by PCR and analysis of antimicrobial resistance.
2001 Dec
Pneumocystis carinii pneumonitis in haemophagocytic lymphohistiocytosis.
2001 Dec
Empirical treatment of uncomplicated urinary tract infection by community pharmacist in the Eastern province of Saudi Arabia.
2001 Dec
Gradient diffusion antibiotic susceptibility testing of potentially probiotic lactobacilli.
2001 Dec
Antibiotic failure in the treatment of urinary tract infections in young women.
2001 Dec
Neonatal brucellosis and blood transfusion: case report and review of the literature.
2001 Dec
Prevalence of antimicrobial resistance in Streptococcus pneumoniae circulating in Italy: results of the Italian Epidemiological Observatory Survey (1997-1999).
2001 Fall
Epidemic of Vibrio cholerae serogroup O139 in Berhampur, Orissa.
2001 Jul
Infectious complications in chronic lymphoid malignancy.
2001 Jun
Antimicrobial sensitivity of Haemophilus influenzae isolates from bacterial conjunctivitis.
2001 Jun
Changing pattern of biotypes, phage types & drug resistance of Salmonella typhi in Ludhiana during 1980-1999.
2001 May
Epidemiology of major respiratory pathogens.
2001 Nov
A common-source water-borne outbreak of multidrug-resistant typhoid fever in a rural Thai community.
2001 Nov
Susceptibility patterns of enteroaggregative Escherichia coli associated with traveller's diarrhoea: emergence of quinolone resistance.
2001 Nov
Co-trimoxazole compared with sulfadoxine-pyrimethamine in the treatment of uncomplicated malaria in Kenyan children.
2001 Nov-Dec
Epidemiological analysis of Salmonella enteritidis isolates in Singapore.
2001 Oct
Susceptibility patterns and serotypes of non-typhoidal salmonella in Trinidad.
2001 Oct
Bacterial aetiology and anti-microbial resistance of childhood diarrhoea in Yemen.
2001 Oct
Epidemiology of shigellosis in Lagos, Nigeria: trends in antimicrobial resistance.
2001 Sep
Occurrence of enteric redmouth disease in rainbow trout (Oncorhynchus mykiss) on farms in Croatia.
2002
[Antibiotic resistance of staphylococci isolated from outpatients].
2002
Staphylococcus aureus and Wegener's granulomatosis.
2002
Incidence and molecular analysis of Vibrio cholerae associated with cholera outbreak subsequent to the super cyclone in Orissa, India.
2002 Apr
[General antibiotic therapy in acne].
2002 Apr 15
Burkholderia pseudomallei: abscess in an unusual site.
2002 Apr-Jun
Pneumocystis carinii: where are we now?
2002 Feb
Clinical efficacy of co-trimoxazole versus amoxicillin twice daily for treatment of pneumonia: a randomised controlled clinical trial in Pakistan.
2002 Feb
Prophylactic antibiotic use in transurethral prostatic resection: a meta-analysis.
2002 Feb
Clinical and biological evolution of HIV-1 seroconverters in Abidjan, Côte d'Ivoire, 1997-2000.
2002 Feb 1
Allergic adverse reactions to sulfonamides.
2002 Jan
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
Prevalence of and resistance to anti-microbial drugs in selected microbial species isolated from bulk milk samples.
2002 Jun
In vitro activities of pentamidine, pyrimethamine, trimethoprim, and sulfonamides against Aspergillus species.
2002 Jun
HIV-1/AIDS and maternal and child health in Africa.
2002 Jun 15
Modified antimicrobial disc susceptibility testing for nutritionally-variant streptococci.
2002 Mar
The relation between sale of antimicrobial drugs and antibiotic resistance in uropathogens in general practice.
2002 Mar
A European study on the relationship between antimicrobial use and antimicrobial resistance.
2002 Mar
Q fever during pregnancy: diagnosis, treatment, and follow-up.
2002 Mar 25
Changes in Escherichia coli resistance to co-trimoxazole in tuberculosis patients and in relation to co-trimoxazole prophylaxis in Thyolo, Malawi.
2002 Mar-Apr
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
Clinical signs and symptoms in the assessment of immunodeficiency in men with subtype C HIV infection in Harare, Zimbabwe.
2002 Mar-Apr
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
Rapid increase in macrolide resistance among penicillin non-susceptible pneumococci in Finland, 1996-2000.
2002 May
Emergence of vancomycin-intermediate Staphylococcus aureus and S. sciuri, Greece.
2002 May
Neutropenic enterocolitis (typhlitis) after pediatric bone marrow transplant.
2002 May
First characterization of a cluster of VanA-type glycopeptide-resistant Enterococcus faecium, Colombia.
2002 Sep
Patents

Sample Use Guides

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
Curator's Comment:: Trimethoprim can be used as an alternative to trimethoprim/sulfamethoxazole based on in vitro antibacterial susceptibility.
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 Jun 25 20:58:25 UTC 2021
Edited
by admin
on Fri Jun 25 20:58:25 UTC 2021
Record UNII
E377MF8EQ8
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TRIMETHOPRIM SULFATE
MART.   ORANGE BOOK   USAN   USP   VANDF   WHO-DD  
USAN  
Official Name English
TRIMETHOPRIM SULFATE [USP MONOGRAPH]
Common Name English
TRIMETHOPRIM SULFATE [USAN]
Common Name English
POLYTRIM COMPONENT TRIMETHOPRIM SULFATE
Common Name English
TRIMETHOPRIM SULFATE [WHO-DD]
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
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
Created by admin on Fri Jun 25 20:58:25 UTC 2021 , Edited by admin on Fri Jun 25 20:58:25 UTC 2021
Code System Code Type Description
PUBCHEM
64936
Created by admin on Fri Jun 25 20:58:25 UTC 2021 , Edited by admin on Fri Jun 25 20:58:25 UTC 2021
PRIMARY
FDA UNII
E377MF8EQ8
Created by admin on Fri Jun 25 20:58:25 UTC 2021 , Edited by admin on Fri Jun 25 20:58:25 UTC 2021
PRIMARY
RXCUI
221176
Created by admin on Fri Jun 25 20:58:25 UTC 2021 , Edited by admin on Fri Jun 25 20:58:25 UTC 2021
PRIMARY RxNorm
EPA CompTox
56585-33-2
Created by admin on Fri Jun 25 20:58:25 UTC 2021 , Edited by admin on Fri Jun 25 20:58:25 UTC 2021
PRIMARY
CAS
56585-33-2
Created by admin on Fri Jun 25 20:58:25 UTC 2021 , Edited by admin on Fri Jun 25 20:58:25 UTC 2021
PRIMARY
ChEMBL
CHEMBL22
Created by admin on Fri Jun 25 20:58:25 UTC 2021 , Edited by admin on Fri Jun 25 20:58:25 UTC 2021
PRIMARY
NCI_THESAURUS
C48028
Created by admin on Fri Jun 25 20:58:25 UTC 2021 , Edited by admin on Fri Jun 25 20:58:25 UTC 2021
PRIMARY
EVMPD
SUB15618MIG
Created by admin on Fri Jun 25 20:58:25 UTC 2021 , Edited by admin on Fri Jun 25 20:58:25 UTC 2021
PRIMARY
DRUG BANK
DBSALT001471
Created by admin on Fri Jun 25 20:58:25 UTC 2021 , Edited by admin on Fri Jun 25 20:58:25 UTC 2021
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY