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 | 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 | ClH |
Molecular Weight | 36.461 |
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 |
---|---|---|
Identification of Cryptosporidium parvum dihydrofolate reductase inhibitors by complementation in Saccharomyces cerevisiae. | 2000 Apr |
|
The pro-apoptotic Bcl-2 family member tBid localizes to mitochondrial contact sites. | 2001 |
|
HIV and drug allergy. | 2001 Aug |
|
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 |
|
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 |
|
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 |
|
Infectious complications in chronic lymphoid malignancy. | 2001 Jun |
|
Synthesis of 2,4-diamino-6-(thioarylmethyl)pyrido[2,3-d]pyrimidines as dihydrofolate reductase inhibitors. | 2001 Nov |
|
Epidemiological analysis of Salmonella enteritidis isolates in Singapore. | 2001 Oct |
|
Isolation of rat dihydrofolate reductase gene and characterization of recombinant enzyme. | 2001 Sep |
|
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 |
|
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 |
|
Allergic adverse reactions to sulfonamides. | 2002 Jan |
|
A double-hand transplant can be worth the effort! | 2002 Jul 15 |
|
Q fever during pregnancy: diagnosis, treatment, and follow-up. | 2002 Mar 25 |
|
Changes in Escherichia coli resistance to co-trimoxazole in tuberculosis patients and in relation to co-trimoxazole prophylaxis in Thyolo, Malawi. | 2002 Mar-Apr |
|
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 15 15:54:37 UTC 2023
by
admin
on
Fri Dec 15 15:54:37 UTC 2023
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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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-
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NCI_THESAURUS |
C2153
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262-450-6
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SUB194326
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DTXSID40209671
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9XE000OU9B
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100000180062
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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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ACTIVE MOIETY |