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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 of TRIMETHOPRIM SULFATE

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

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

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
Synthesis and biological evaluation of 5-arylfuro[2,3-d]pyrimidines as novel dihydrofolate reductase inhibitors.
1999 Feb
Interleukin 6 may be an important mediator of trimethoprim-induced systemic adverse reaction resembling aseptic meningitis.
2000 Jul 10
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
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
[Antimicrobial therapy of urinary tract infections].
2001 Jan-Feb
Pulmonary nocardiosis in human immunodeficiency virus infection: a tuberculosis mimic.
2001 Jan-Mar
Public health lessons from a pilot programme to reduce mother-to-child transmission of HIV-1 in Khayelitsha.
2001 Jul
Etiologies of the urinary tract infections in a Yemeni City.
2001 Jul
Successful therapy combined with surgery for severe post-transplant nocardiosis.
2001 Jul-Aug
Infectious complications in chronic lymphoid malignancy.
2001 Jun
Initiating co-trimoxazole prophylaxis in HIV-infected patients in Africa: an evaluation of the provisional WHO/UNAIDS recommendations.
2001 Jun 15
Epidemiology of major respiratory pathogens.
2001 Nov
Incidence and risk factors for the development of indinavir-associated renal complications.
2001 Sep
Isolation of rat dihydrofolate reductase gene and characterization of recombinant enzyme.
2001 Sep
Shigellosis linked to sex venues, Australia.
2002 Aug
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
A double-hand transplant can be worth the effort!
2002 Jul 15
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
Q fever during pregnancy: diagnosis, treatment, and follow-up.
2002 Mar 25
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
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 Wed Jul 05 22:53:08 UTC 2023
Edited
by admin
on Wed Jul 05 22:53:08 UTC 2023
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 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
Created by admin on Wed Jul 05 22:53:08 UTC 2023 , Edited by admin on Wed Jul 05 22:53:08 UTC 2023
Code System Code Type Description
PUBCHEM
64936
Created by admin on Wed Jul 05 22:53:08 UTC 2023 , Edited by admin on Wed Jul 05 22:53:08 UTC 2023
PRIMARY
FDA UNII
E377MF8EQ8
Created by admin on Wed Jul 05 22:53:08 UTC 2023 , Edited by admin on Wed Jul 05 22:53:08 UTC 2023
PRIMARY
USAN
U-99
Created by admin on Wed Jul 05 22:53:08 UTC 2023 , Edited by admin on Wed Jul 05 22:53:08 UTC 2023
PRIMARY
DAILYMED
E377MF8EQ8
Created by admin on Wed Jul 05 22:53:08 UTC 2023 , Edited by admin on Wed Jul 05 22:53:08 UTC 2023
PRIMARY
RXCUI
221176
Created by admin on Wed Jul 05 22:53:08 UTC 2023 , Edited by admin on Wed Jul 05 22:53:08 UTC 2023
PRIMARY RxNorm
SMS_ID
100000077297
Created by admin on Wed Jul 05 22:53:08 UTC 2023 , Edited by admin on Wed Jul 05 22:53:08 UTC 2023
PRIMARY
EPA CompTox
DTXSID40205138
Created by admin on Wed Jul 05 22:53:08 UTC 2023 , Edited by admin on Wed Jul 05 22:53:08 UTC 2023
PRIMARY
CAS
56585-33-2
Created by admin on Wed Jul 05 22:53:08 UTC 2023 , Edited by admin on Wed Jul 05 22:53:08 UTC 2023
PRIMARY
ChEMBL
CHEMBL22
Created by admin on Wed Jul 05 22:53:08 UTC 2023 , Edited by admin on Wed Jul 05 22:53:08 UTC 2023
PRIMARY
NCI_THESAURUS
C48028
Created by admin on Wed Jul 05 22:53:08 UTC 2023 , Edited by admin on Wed Jul 05 22:53:08 UTC 2023
PRIMARY
EVMPD
SUB15618MIG
Created by admin on Wed Jul 05 22:53:08 UTC 2023 , Edited by admin on Wed Jul 05 22:53:08 UTC 2023
PRIMARY
DRUG BANK
DBSALT001471
Created by admin on Wed Jul 05 22:53:08 UTC 2023 , Edited by admin on Wed Jul 05 22:53:08 UTC 2023
PRIMARY
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