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

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
Structure of TRIMETHOPRIM LACTATE

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)

HIDE SMILES / InChI

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 ( + / - )

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
Susceptibilities of Mycobacterium tuberculosis and Mycobacterium avium complex to lipophilic deazapteridine derivatives, inhibitors of dihydrofolate reductase.
1998 Dec
A report case of Cyclospora and Cryptosporidium mixed infection in a HIV-negative child in Thailand.
2001 Apr
Prevalence of resistance to antimicrobials of Escherichia coli isolates from clinical sources at a private hospital in Trinidad.
2001 Apr
Predominance of a methicillin-resistant Staphylococcus aureus clone susceptible to erythromycin and several other non-beta-lactam antibiotics in a Greek hospital.
2001 Aug
Antimicrobial resistance of Shigella spp isolated from diarrheal patients between 1989 and 1998 in Vietnam.
2001 Dec
Empirical treatment of uncomplicated urinary tract infection by community pharmacist in the Eastern province of Saudi Arabia.
2001 Dec
Antibiotic failure in the treatment of urinary tract infections in young women.
2001 Dec
Prevalence of antimicrobial resistance in Streptococcus pneumoniae circulating in Italy: results of the Italian Epidemiological Observatory Survey (1997-1999).
2001 Fall
Antimicrobial activities of dihydrofolate reductase inhibitors, used singly or in combination with dapsone, against Mycobacterium ulcerans.
2001 Jan
[Antimicrobial therapy of urinary tract infections].
2001 Jan-Feb
Brucellosis in children of Dhofar Region, Oman.
2001 Jul
Consensus on use of co-trimoxazole.
2001 Jul
Pneumocystis carinii pneumonia in patients being registered for smear-negative pulmonary tuberculosis in Malawi.
2001 Jul-Aug
Successful therapy combined with surgery for severe post-transplant nocardiosis.
2001 Jul-Aug
Initiating co-trimoxazole prophylaxis in HIV-infected patients in Africa: an evaluation of the provisional WHO/UNAIDS recommendations.
2001 Jun 15
Association between tuberculosis and HIV disease progression in a high tuberculosis prevalence area.
2001 Mar
Co-trimoxazole and genital ulceration.
2001 Mar
A common-source water-borne outbreak of multidrug-resistant typhoid fever in a rural Thai community.
2001 Nov
Synthesis of 2,4-diamino-6-(thioarylmethyl)pyrido[2,3-d]pyrimidines as dihydrofolate reductase inhibitors.
2001 Nov
Co-trimoxazole compared with sulfadoxine-pyrimethamine in the treatment of uncomplicated malaria in Kenyan children.
2001 Nov-Dec
Epidemiology of shigellosis in Lagos, Nigeria: trends in antimicrobial resistance.
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
Incidence and molecular analysis of Vibrio cholerae associated with cholera outbreak subsequent to the super cyclone in Orissa, India.
2002 Apr
Burkholderia pseudomallei: abscess in an unusual site.
2002 Apr-Jun
Pneumocystis carinii: where are we now?
2002 Feb
Clinical efficacy of co-trimoxazole versus amoxicillin twice daily for treatment of pneumonia: a randomised controlled clinical trial in Pakistan.
2002 Feb
Prevalence of and resistance to anti-microbial drugs in selected microbial species isolated from bulk milk samples.
2002 Jun
Clinical signs and symptoms in the assessment of immunodeficiency in men with subtype C HIV infection in Harare, Zimbabwe.
2002 Mar-Apr
Urinary tract-derived Escherichia coli resistant to co-trimoxazole in Japan, where the drug is seldom used for treating acute urinary tract infections.
2002 May
Rapid increase in macrolide resistance among penicillin non-susceptible pneumococci in Finland, 1996-2000.
2002 May
Neutropenic enterocolitis (typhlitis) after pediatric bone marrow transplant.
2002 May
First characterization of a cluster of VanA-type glycopeptide-resistant Enterococcus faecium, Colombia.
2002 Sep
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 Fri Dec 16 17:04:43 UTC 2022
Edited
by admin
on Fri Dec 16 17:04:43 UTC 2022
Record UNII
P3K8GP9FDQ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TRIMETHOPRIM LACTATE
WHO-DD  
Common Name English
2,4-PYRIMIDINEDIAMINE, 5-((3,4,5-TRIMETHOXYPHENYL)METHYL)-, MONO(2-HYDROXYPROPANOATE)
Common Name English
Trimethoprim lactate [WHO-DD]
Common Name English
PROPANOIC ACID, 2-HYDROXY-, COMPD. WITH 5-((3,4,5-TRIMETHOXYPHENYL)METHYL)-2,4-PYRIMIDINEDIAMINE (1:1)
Common Name English
LACTOTRIM
Brand Name English
LACTIC ACID, COMPD. WITH 2,4-DIAMINO-5-(3,4,5-TRIMETHOXYBENZYL)PYRIMIDINE (1:1)
Common Name English
Code System Code Type Description
EVMPD
SUB04972MIG
Created by admin on Fri Dec 16 17:04:43 UTC 2022 , Edited by admin on Fri Dec 16 17:04:43 UTC 2022
PRIMARY
ECHA (EC/EINECS)
245-533-1
Created by admin on Fri Dec 16 17:04:43 UTC 2022 , Edited by admin on Fri Dec 16 17:04:43 UTC 2022
PRIMARY
RXCUI
235855
Created by admin on Fri Dec 16 17:04:43 UTC 2022 , Edited by admin on Fri Dec 16 17:04:43 UTC 2022
PRIMARY RxNorm
FDA UNII
P3K8GP9FDQ
Created by admin on Fri Dec 16 17:04:43 UTC 2022 , Edited by admin on Fri Dec 16 17:04:43 UTC 2022
PRIMARY
CAS
23256-42-0
Created by admin on Fri Dec 16 17:04:43 UTC 2022 , Edited by admin on Fri Dec 16 17:04:43 UTC 2022
PRIMARY
EPA CompTox
DTXSID00945947
Created by admin on Fri Dec 16 17:04:43 UTC 2022 , Edited by admin on Fri Dec 16 17:04:43 UTC 2022
PRIMARY
PUBCHEM
3084396
Created by admin on Fri Dec 16 17:04:43 UTC 2022 , Edited by admin on Fri Dec 16 17:04:43 UTC 2022
PRIMARY
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