Details
Stereochemistry | ACHIRAL |
Molecular Formula | C14H18N4O3.ClH |
Molecular Weight | 326.779 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.COC1=CC(CC2=C(N)N=C(N)N=C2)=CC(OC)=C1OC
InChI
InChIKey=YLCCEQZHUHUYPA-UHFFFAOYSA-N
InChI=1S/C14H18N4O3.ClH/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);1H
Molecular Formula | ClH |
Molecular Weight | 36.461 |
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 |
---|---|---|
Susceptibilities of Mycobacterium tuberculosis and Mycobacterium avium complex to lipophilic deazapteridine derivatives, inhibitors of dihydrofolate reductase. | 1998 Dec |
|
Synthesis and biological evaluation of 5-arylfuro[2,3-d]pyrimidines as novel dihydrofolate reductase inhibitors. | 1999 Feb |
|
Three-dimensional structure of M. tuberculosis dihydrofolate reductase reveals opportunities for the design of novel tuberculosis drugs. | 2000 Jan 14 |
|
Prevalence of resistance to antimicrobials of Escherichia coli isolates from clinical sources at a private hospital in Trinidad. | 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 |
|
Antimicrobial resistance of Shigella spp isolated from diarrheal patients between 1989 and 1998 in Vietnam. | 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 |
|
Neonatal brucellosis and blood transfusion: case report and review of the literature. | 2001 Dec |
|
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 |
|
Infectious complications in chronic lymphoid malignancy. | 2001 Jun |
|
Successful management of Brucella mellitensis endocarditis with combined medical and surgical approach. | 2001 Jun |
|
Patterns of antibiotic resistance, serotype distribution, and patient demographics of Streptococcus pneumoniae in Hong Kong. | 2001 Mar-Apr |
|
Changing pattern of biotypes, phage types & drug resistance of Salmonella typhi in Ludhiana during 1980-1999. | 2001 May |
|
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 |
|
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 |
|
Occurrence of enteric redmouth disease in rainbow trout (Oncorhynchus mykiss) on farms in Croatia. | 2002 |
|
Burkholderia pseudomallei: abscess in an unusual site. | 2002 Apr-Jun |
|
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 |
|
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 |
|
The relation between sale of antimicrobial drugs and antibiotic resistance in uropathogens in general practice. | 2002 Mar |
|
Emergence of vancomycin-intermediate Staphylococcus aureus and S. sciuri, Greece. | 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 18:35:43 UTC 2022
by
admin
on
Fri Dec 16 18:35:43 UTC 2022
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Record UNII |
9XE000OU9B
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Record Status |
Validated (UNII)
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Record Version |
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Common Name | English |
Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C2153
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262-450-6
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9XE000OU9B
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SUB194326
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DTXSID40209671
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9XE000OU9B
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259281
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60834-30-2
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173769
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DBSALT001480
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CHEMBL22
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Trimethoprim hydrochloride
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C77554
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PARENT -> SALT/SOLVATE |
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ACTIVE MOIETY |