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 |
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 |
|---|---|---|
| Three-dimensional structure of M. tuberculosis dihydrofolate reductase reveals opportunities for the design of novel tuberculosis drugs. | 2000 Jan 14 |
|
| Interleukin 6 may be an important mediator of trimethoprim-induced systemic adverse reaction resembling aseptic meningitis. | 2000 Jul 10 |
|
| 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 |
|
| Aminopyrimidine-carboxyl(ate) interactions in trimethoprim maleate, an antifolate drug. | 2001 Apr |
|
| [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 |
|
| 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 |
|
| Gradient diffusion antibiotic susceptibility testing of potentially probiotic lactobacilli. | 2001 Dec |
|
| Prevalence of antimicrobial resistance in Streptococcus pneumoniae circulating in Italy: results of the Italian Epidemiological Observatory Survey (1997-1999). | 2001 Fall |
|
| Bsoft: image and molecular processing in electron microscopy. | 2001 Feb-Mar |
|
| Antistaphylococcal (MSSA, MRSA, MSSE, MRSE) antibiotics. | 2001 Jan |
|
| 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 |
|
| Brucellosis in children of Dhofar Region, Oman. | 2001 Jul |
|
| Etiologies of the urinary tract infections in a Yemeni City. | 2001 Jul |
|
| Successful treatment of late onset infection due to multi-drug resistant Acinetobacter Lwoffii in a low birth weight neonate using ciprofloxacin. | 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 |
|
| Epidemiology of major respiratory pathogens. | 2001 Nov |
|
| 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 |
|
| Epidemiology of shigellosis in Lagos, Nigeria: trends in antimicrobial resistance. | 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 |
|
| 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 |
|
| Staphylococcus aureus and Wegener's granulomatosis. | 2002 |
|
| Shigellosis linked to sex venues, Australia. | 2002 Aug |
|
| Prophylactic antibiotic use in transurethral prostatic resection: a meta-analysis. | 2002 Feb |
|
| 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 |
|
| HIV-1/AIDS and maternal and child health in Africa. | 2002 Jun 15 |
|
| Q fever during pregnancy: diagnosis, treatment, and follow-up. | 2002 Mar 25 |
|
| Rapid increase in macrolide resistance among penicillin non-susceptible pneumococci in Finland, 1996-2000. | 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
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
Wed Jul 05 23:23:03 UTC 2023
by
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on
Wed Jul 05 23:23:03 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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NCI_THESAURUS |
C2153
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262-450-6
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SUB194326
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DTXSID40209671
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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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PARENT -> SALT/SOLVATE |
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ACTIVE MOIETY |