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 | C14H18N4O3 |
Molecular Weight | 290.3177 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
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 | ( + / - ) |
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 Date1982 |
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 |
|
Identification of Cryptosporidium parvum dihydrofolate reductase inhibitors by complementation in Saccharomyces cerevisiae. | 2000 Apr |
|
Interleukin 6 may be an important mediator of trimethoprim-induced systemic adverse reaction resembling aseptic meningitis. | 2000 Jul 10 |
|
Design, synthesis, and X-ray crystal structure of a potent dual inhibitor of thymidylate synthase and dihydrofolate reductase as an antitumor agent. | 2000 Oct 19 |
|
The pro-apoptotic Bcl-2 family member tBid localizes to mitochondrial contact sites. | 2001 |
|
[High sensitivity of Escherichia coli to antimicrobial agents used for first-line treatment of urinary tract infections; results of an examination of feces of healthy subjects in Friesland]. | 2001 Apr 7 |
|
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 |
|
Effect of mutations in Pneumocystis carinii dihydropteroate synthase gene on outcome of P carinii pneumonia in patients with HIV-1: a prospective study. | 2001 Aug 18 |
|
Rapid detection of Haemophilus influenzae type b in Bangladeshi children with pneumonia and meningitis by PCR and analysis of antimicrobial resistance. | 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 |
|
Properties of multidrug-resistant, ESBL-producing Proteus mirabilis isolates and possible role of beta-lactam/beta-lactamase inhibitor combinations. | 2001 Feb |
|
Antistaphylococcal (MSSA, MRSA, MSSE, MRSE) antibiotics. | 2001 Jan |
|
Antimicrobial activities of dihydrofolate reductase inhibitors, used singly or in combination with dapsone, against Mycobacterium ulcerans. | 2001 Jan |
|
Travel-associated Burkholderia pseudomallei infection (Melioidosis) in a patient with cystic fibrosis: a case report. | 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 |
|
Public health lessons from a pilot programme to reduce mother-to-child transmission of HIV-1 in Khayelitsha. | 2001 Jul |
|
Pneumocystis carinii pneumonia in patients being registered for smear-negative pulmonary tuberculosis in Malawi. | 2001 Jul-Aug |
|
Bacteriuria in the elderly population in a developing country. | 2001 Jul-Aug |
|
Successful treatment of late onset infection due to multi-drug resistant Acinetobacter Lwoffii in a low birth weight neonate using ciprofloxacin. | 2001 Jun |
|
Successful management of Brucella mellitensis endocarditis with combined medical and surgical approach. | 2001 Jun |
|
Initiating co-trimoxazole prophylaxis in HIV-infected patients in Africa: an evaluation of the provisional WHO/UNAIDS recommendations. | 2001 Jun 15 |
|
Susceptibility patterns of enteroaggregative Escherichia coli associated with traveller's diarrhoea: emergence of quinolone resistance. | 2001 Nov |
|
Susceptibility patterns and serotypes of non-typhoidal salmonella in Trinidad. | 2001 Oct |
|
Use of systemic anti-infective agents in Iran during 1997-1998. | 2001 Sep |
|
Antibiotic use and resistance of Streptococcus pneumoniae in The Netherlands during the period 1994-1999. | 2001 Sep |
|
Incidence and risk factors for the development of indinavir-associated renal complications. | 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 |
|
Trimethoprim-induced aseptic meningitis in an adolescent male. | 2002 Aug |
|
Allergic adverse reactions to sulfonamides. | 2002 Jan |
|
HIV-1/AIDS and maternal and child health in Africa. | 2002 Jun 15 |
|
A disseminated multidrug-resistant clonal group of uropathogenic Escherichia coli in pyelonephritis. | 2002 Jun 29 |
|
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 |
|
Neutropenic enterocolitis (typhlitis) after pediatric bone marrow transplant. | 2002 May |
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
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Edited
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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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100000084666
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SUB04972MIG
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245-533-1
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DTXSID00945947
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