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
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)
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
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2364669 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19622858 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Curative | TRIMETHOPRIM Approved UseTo 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 Date3.96748784E11 |
Cmax
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 |
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 |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
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: |
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 Health Status: unhealthy Sources: |
Other AEs: Nausea, Vomiting... Other AEs: Nausea Sources: Vomiting Dizziness Headaches Confusion Bone marrow depression |
AEs
AE | Significance | 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: |
unhealthy Health Status: unhealthy Sources: |
|
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 Health Status: unhealthy Sources: |
|
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 Health Status: unhealthy Sources: |
|
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 Health Status: unhealthy Sources: |
|
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 Health Status: unhealthy Sources: |
|
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 Health Status: unhealthy Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical 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 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/|https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1884466/ Page: 4.0 |
|||
yes [IC50 1318 uM] | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4 |
yes [Inhibition 250 uM] | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4 |
yes [Inhibition 250 uM] | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4 |
yes [Inhibition 250 uM] | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4 |
yes [Inhibition 250 uM] | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4 |
yes [Inhibition <250 uM] | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4 |
yes [Inhibition <250 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes |
PubMed
Title | Date | PubMed |
---|---|---|
The pro-apoptotic Bcl-2 family member tBid localizes to mitochondrial contact sites. | 2001 |
|
Clinical significance and impact on mortality of extended-spectrum beta lactamase-producing Enterobacteriaceae isolates in nosocomial bacteremia. | 2001 |
|
A report case of Cyclospora and Cryptosporidium mixed infection in a HIV-negative child in Thailand. | 2001 Apr |
|
[Whipple disease and non-Hodgkin lymphoma]. | 2001 Apr |
|
Aminopyrimidine-carboxyl(ate) interactions in trimethoprim maleate, an antifolate drug. | 2001 Apr |
|
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 |
|
Predominance of a methicillin-resistant Staphylococcus aureus clone susceptible to erythromycin and several other non-beta-lactam antibiotics in a Greek hospital. | 2001 Aug |
|
Effects of trimethoprim and co-trimoxazole on the morphology of Listeria monocytogenes in culture medium and after phagocytosis. | 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 |
|
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 |
|
Co-trimoxazole resistant Brucella. | 2001 Feb |
|
Bsoft: image and molecular processing in electron microscopy. | 2001 Feb-Mar |
|
Antistaphylococcal (MSSA, MRSA, MSSE, MRSE) antibiotics. | 2001 Jan |
|
[Antimicrobial therapy of urinary tract infections]. | 2001 Jan-Feb |
|
Pulmonary nocardiosis in human immunodeficiency virus infection: a tuberculosis mimic. | 2001 Jan-Mar |
|
Epidemic of Vibrio cholerae serogroup O139 in Berhampur, Orissa. | 2001 Jul |
|
Brucellosis in children of Dhofar Region, Oman. | 2001 Jul |
|
Etiologies of the urinary tract infections in a Yemeni City. | 2001 Jul |
|
Pneumocystis carinii pneumonia in patients being registered for smear-negative pulmonary tuberculosis in Malawi. | 2001 Jul-Aug |
|
Successful therapy combined with surgery for severe post-transplant nocardiosis. | 2001 Jul-Aug |
|
Bacteriuria in the elderly population in a developing country. | 2001 Jul-Aug |
|
Infectious complications in chronic lymphoid malignancy. | 2001 Jun |
|
Successful management of Brucella mellitensis endocarditis with combined medical and surgical approach. | 2001 Jun |
|
Association between tuberculosis and HIV disease progression in a high tuberculosis prevalence area. | 2001 Mar |
|
Co-trimoxazole and genital ulceration. | 2001 Mar |
|
Patterns of antibiotic resistance, serotype distribution, and patient demographics of Streptococcus pneumoniae in Hong Kong. | 2001 Mar-Apr |
|
Effect of early chemoprophylaxis with co-trimoxazole on nutritional status evolution in HIV-1-infected adults in Abidjan, Côte d'Ivoire. | 2001 May 4 |
|
A common-source water-borne outbreak of multidrug-resistant typhoid fever in a rural Thai community. | 2001 Nov |
|
Synthesis of 2,4-diamino-6-(thioarylmethyl)pyrido[2,3-d]pyrimidines as dihydrofolate reductase inhibitors. | 2001 Nov |
|
Co-trimoxazole compared with sulfadoxine-pyrimethamine in the treatment of uncomplicated malaria in Kenyan children. | 2001 Nov-Dec |
|
Bacterial aetiology and anti-microbial resistance of childhood diarrhoea in Yemen. | 2001 Oct |
|
Antibiotic use and resistance of Streptococcus pneumoniae in The Netherlands during the period 1994-1999. | 2001 Sep |
|
In vitro activity of novel fluoroquinolones against Streptococcus pneumoniae isolated from children with acute otitis media. | 2001 Sep-Oct |
|
Developing and testing instruments to measure client outcomes at the Comox Valley Nursing Center. | 2001 Sep-Oct |
|
Occurrence of enteric redmouth disease in rainbow trout (Oncorhynchus mykiss) on farms in Croatia. | 2002 |
|
[Antibiotic resistance of staphylococci isolated from outpatients]. | 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 |
|
Shigellosis linked to sex venues, Australia. | 2002 Aug |
|
Allergic adverse reactions to sulfonamides. | 2002 Jan |
|
Facilitating changes in perinatal smoking. The impact of a stage-based workshop for care-providers in British Columbia. | 2002 Jul-Aug |
|
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 |
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20488468
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
Edited
Fri Dec 16 16:55:52 UTC 2022
by
admin
on
Fri Dec 16 16:55:52 UTC 2022
|
Record UNII |
E377MF8EQ8
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Common Name | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
NCI_THESAURUS |
C255
Created by
admin on Fri Dec 16 16:55:52 UTC 2022 , Edited by admin on Fri Dec 16 16:55:52 UTC 2022
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
64936
Created by
admin on Fri Dec 16 16:55:52 UTC 2022 , Edited by admin on Fri Dec 16 16:55:52 UTC 2022
|
PRIMARY | |||
|
E377MF8EQ8
Created by
admin on Fri Dec 16 16:55:52 UTC 2022 , Edited by admin on Fri Dec 16 16:55:52 UTC 2022
|
PRIMARY | |||
|
U-99
Created by
admin on Fri Dec 16 16:55:52 UTC 2022 , Edited by admin on Fri Dec 16 16:55:52 UTC 2022
|
PRIMARY | |||
|
E377MF8EQ8
Created by
admin on Fri Dec 16 16:55:52 UTC 2022 , Edited by admin on Fri Dec 16 16:55:52 UTC 2022
|
PRIMARY | |||
|
221176
Created by
admin on Fri Dec 16 16:55:52 UTC 2022 , Edited by admin on Fri Dec 16 16:55:52 UTC 2022
|
PRIMARY | RxNorm | ||
|
DTXSID40205138
Created by
admin on Fri Dec 16 16:55:52 UTC 2022 , Edited by admin on Fri Dec 16 16:55:52 UTC 2022
|
PRIMARY | |||
|
56585-33-2
Created by
admin on Fri Dec 16 16:55:52 UTC 2022 , Edited by admin on Fri Dec 16 16:55:52 UTC 2022
|
PRIMARY | |||
|
CHEMBL22
Created by
admin on Fri Dec 16 16:55:52 UTC 2022 , Edited by admin on Fri Dec 16 16:55:52 UTC 2022
|
PRIMARY | |||
|
C48028
Created by
admin on Fri Dec 16 16:55:52 UTC 2022 , Edited by admin on Fri Dec 16 16:55:52 UTC 2022
|
PRIMARY | |||
|
SUB15618MIG
Created by
admin on Fri Dec 16 16:55:52 UTC 2022 , Edited by admin on Fri Dec 16 16:55:52 UTC 2022
|
PRIMARY | |||
|
DBSALT001471
Created by
admin on Fri Dec 16 16:55:52 UTC 2022 , Edited by admin on Fri Dec 16 16:55:52 UTC 2022
|
PRIMARY |
Related Record | Type | Details | ||
---|---|---|---|---|
|
PARENT -> SALT/SOLVATE |
Related Record | Type | Details | ||
---|---|---|---|---|
|
ACTIVE MOIETY |