Details
| Stereochemistry | RACEMIC |
| Molecular Formula | C14H18N4O3.C3H6O3 |
| Molecular Weight | 380.3957 |
| Optical Activity | ( + / - ) |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(O)C(O)=O.COC1=CC(CC2=C(N)N=C(N)N=C2)=CC(OC)=C1OC
InChI
InChIKey=IIZVTUWSIKTFKO-UHFFFAOYSA-N
InChI=1S/C14H18N4O3.C3H6O3/c1-19-10-5-8(6-11(20-2)12(10)21-3)4-9-7-17-14(16)18-13(9)15;1-2(4)3(5)6/h5-7H,4H2,1-3H3,(H4,15,16,17,18);2,4H,1H3,(H,5,6)
| Molecular Formula | C3H6O3 |
| Molecular Weight | 90.0779 |
| Charge | 0 |
| Count |
|
| Stereochemistry | RACEMIC |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Optical Activity | ( + / - ) |
| 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 |
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] | ||||
Page: 2,4 |
yes [Inhibition 250 uM] | |||
Page: 2,4 |
yes [Inhibition 250 uM] | |||
Page: 2,4 |
yes [Inhibition 250 uM] | |||
Page: 2,4 |
yes [Inhibition 250 uM] | |||
Page: 2,4 |
yes [Inhibition <250 uM] | |||
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 |
|---|---|---|
| Susceptibilities of Mycobacterium tuberculosis and Mycobacterium avium complex to lipophilic deazapteridine derivatives, inhibitors of dihydrofolate reductase. | 1998 Dec |
|
| A report case of Cyclospora and Cryptosporidium mixed infection in a HIV-negative child in Thailand. | 2001 Apr |
|
| Prevalence of resistance to antimicrobials of Escherichia coli isolates from clinical sources at a private hospital in Trinidad. | 2001 Apr |
|
| Predominance of a methicillin-resistant Staphylococcus aureus clone susceptible to erythromycin and several other non-beta-lactam antibiotics in a Greek hospital. | 2001 Aug |
|
| Antimicrobial resistance of Shigella spp isolated from diarrheal patients between 1989 and 1998 in Vietnam. | 2001 Dec |
|
| Empirical treatment of uncomplicated urinary tract infection by community pharmacist in the Eastern province of Saudi Arabia. | 2001 Dec |
|
| Antibiotic failure in the treatment of urinary tract infections in young women. | 2001 Dec |
|
| Prevalence of antimicrobial resistance in Streptococcus pneumoniae circulating in Italy: results of the Italian Epidemiological Observatory Survey (1997-1999). | 2001 Fall |
|
| Antimicrobial activities of dihydrofolate reductase inhibitors, used singly or in combination with dapsone, against Mycobacterium ulcerans. | 2001 Jan |
|
| [Antimicrobial therapy of urinary tract infections]. | 2001 Jan-Feb |
|
| Brucellosis in children of Dhofar Region, Oman. | 2001 Jul |
|
| Consensus on use of co-trimoxazole. | 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 |
|
| Initiating co-trimoxazole prophylaxis in HIV-infected patients in Africa: an evaluation of the provisional WHO/UNAIDS recommendations. | 2001 Jun 15 |
|
| Association between tuberculosis and HIV disease progression in a high tuberculosis prevalence area. | 2001 Mar |
|
| Co-trimoxazole and genital ulceration. | 2001 Mar |
|
| 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 |
|
| Epidemiology of shigellosis in Lagos, Nigeria: trends in antimicrobial resistance. | 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 |
|
| Incidence and molecular analysis of Vibrio cholerae associated with cholera outbreak subsequent to the super cyclone in Orissa, India. | 2002 Apr |
|
| 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 |
|
| Prevalence of and resistance to anti-microbial drugs in selected microbial species isolated from bulk milk samples. | 2002 Jun |
|
| 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 |
|
| 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
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
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admin
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Edited
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by
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Fri Dec 16 17:04:43 UTC 2022
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| Record UNII |
P3K8GP9FDQ
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| Record Status |
Validated (UNII)
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| Record Version |
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SUB04972MIG
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245-533-1
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235855
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P3K8GP9FDQ
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23256-42-0
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DTXSID00945947
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3084396
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