U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
Structure of TRIMETHOPRIM HYDROCHLORIDE

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

HIDE SMILES / InChI

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

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
TRIMETHOPRIM

Approved Use

To 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 Date

3.96748784E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2.1 μg/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
30.7 μg × h/mL
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

T1/2

ValueDoseCo-administeredAnalytePopulation
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

Funbound

ValueDoseCo-administeredAnalytePopulation
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

Doses

DosePopulationAdverse 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
Other AEs: Nausea, Vomiting...
Other AEs:
Nausea
Vomiting
Dizziness
Headaches
Confusion
Bone marrow depression
Sources:
AEs

AEs

AESignificanceDosePopulation
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
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
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
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
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
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
Overview

Overview

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical 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
Page: 4.0
yes [IC50 1318 uM]
yes [Inhibition 250 uM]
yes [Inhibition 250 uM]
yes [Inhibition 250 uM]
yes [Inhibition 250 uM]
yes [Inhibition <250 uM]
yes [Inhibition <250 uM]
Drug as victim
PubMed

PubMed

TitleDatePubMed
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
Patents

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 Wed Jul 05 23:23:03 UTC 2023
Edited
by admin
on Wed Jul 05 23:23:03 UTC 2023
Record UNII
9XE000OU9B
Record Status Validated (UNII)
Record Version
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Name Type Language
TRIMETHOPRIM HYDROCHLORIDE
ORANGE BOOK   WHO-DD  
Common Name English
TRIMETHOPRIM HYDROCHLORIDE [ORANGE BOOK]
Common Name English
TRIMETHOPRIM HCL
Common Name English
Trimethoprim hydrochloride [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C2153
Created by admin on Wed Jul 05 23:23:03 UTC 2023 , Edited by admin on Wed Jul 05 23:23:03 UTC 2023
Code System Code Type Description
ECHA (EC/EINECS)
262-450-6
Created by admin on Wed Jul 05 23:23:03 UTC 2023 , Edited by admin on Wed Jul 05 23:23:03 UTC 2023
PRIMARY
EVMPD
SUB194326
Created by admin on Wed Jul 05 23:23:03 UTC 2023 , Edited by admin on Wed Jul 05 23:23:03 UTC 2023
PRIMARY
EPA CompTox
DTXSID40209671
Created by admin on Wed Jul 05 23:23:03 UTC 2023 , Edited by admin on Wed Jul 05 23:23:03 UTC 2023
PRIMARY
FDA UNII
9XE000OU9B
Created by admin on Wed Jul 05 23:23:03 UTC 2023 , Edited by admin on Wed Jul 05 23:23:03 UTC 2023
PRIMARY
SMS_ID
100000180062
Created by admin on Wed Jul 05 23:23:03 UTC 2023 , Edited by admin on Wed Jul 05 23:23:03 UTC 2023
PRIMARY
RXCUI
259281
Created by admin on Wed Jul 05 23:23:03 UTC 2023 , Edited by admin on Wed Jul 05 23:23:03 UTC 2023
PRIMARY RxNorm
CAS
60834-30-2
Created by admin on Wed Jul 05 23:23:03 UTC 2023 , Edited by admin on Wed Jul 05 23:23:03 UTC 2023
PRIMARY
PUBCHEM
173769
Created by admin on Wed Jul 05 23:23:03 UTC 2023 , Edited by admin on Wed Jul 05 23:23:03 UTC 2023
PRIMARY
DRUG BANK
DBSALT001480
Created by admin on Wed Jul 05 23:23:03 UTC 2023 , Edited by admin on Wed Jul 05 23:23:03 UTC 2023
PRIMARY
ChEMBL
CHEMBL22
Created by admin on Wed Jul 05 23:23:03 UTC 2023 , Edited by admin on Wed Jul 05 23:23:03 UTC 2023
PRIMARY
WIKIPEDIA
Trimethoprim hydrochloride
Created by admin on Wed Jul 05 23:23:03 UTC 2023 , Edited by admin on Wed Jul 05 23:23:03 UTC 2023
PRIMARY
NCI_THESAURUS
C77554
Created by admin on Wed Jul 05 23:23:03 UTC 2023 , Edited by admin on Wed Jul 05 23:23:03 UTC 2023
PRIMARY
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