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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
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
Three-dimensional structure of M. tuberculosis dihydrofolate reductase reveals opportunities for the design of novel tuberculosis drugs.
2000 Jan 14
Prevalence of resistance to antimicrobials of Escherichia coli isolates from clinical sources at a private hospital in Trinidad.
2001 Apr
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
Antimicrobial resistance of Shigella spp isolated from diarrheal patients between 1989 and 1998 in Vietnam.
2001 Dec
Pneumocystis carinii pneumonitis in haemophagocytic lymphohistiocytosis.
2001 Dec
Empirical treatment of uncomplicated urinary tract infection by community pharmacist in the Eastern province of Saudi Arabia.
2001 Dec
Neonatal brucellosis and blood transfusion: case report and review of the literature.
2001 Dec
Public health lessons from a pilot programme to reduce mother-to-child transmission of HIV-1 in Khayelitsha.
2001 Jul
Etiologies of the urinary tract infections in a Yemeni City.
2001 Jul
Infectious complications in chronic lymphoid malignancy.
2001 Jun
Successful management of Brucella mellitensis endocarditis with combined medical and surgical approach.
2001 Jun
Patterns of antibiotic resistance, serotype distribution, and patient demographics of Streptococcus pneumoniae in Hong Kong.
2001 Mar-Apr
Changing pattern of biotypes, phage types & drug resistance of Salmonella typhi in Ludhiana during 1980-1999.
2001 May
Effect of early chemoprophylaxis with co-trimoxazole on nutritional status evolution in HIV-1-infected adults in Abidjan, Côte d'Ivoire.
2001 May 4
A common-source water-borne outbreak of multidrug-resistant typhoid fever in a rural Thai community.
2001 Nov
Co-trimoxazole compared with sulfadoxine-pyrimethamine in the treatment of uncomplicated malaria in Kenyan children.
2001 Nov-Dec
Epidemiological analysis of Salmonella enteritidis isolates in Singapore.
2001 Oct
Susceptibility patterns and serotypes of non-typhoidal salmonella in Trinidad.
2001 Oct
Occurrence of enteric redmouth disease in rainbow trout (Oncorhynchus mykiss) on farms in Croatia.
2002
Burkholderia pseudomallei: abscess in an unusual site.
2002 Apr-Jun
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
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
The relation between sale of antimicrobial drugs and antibiotic resistance in uropathogens in general practice.
2002 Mar
Emergence of vancomycin-intermediate Staphylococcus aureus and S. sciuri, Greece.
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 18:35:43 UTC 2022
Edited
by admin
on Fri Dec 16 18:35:43 UTC 2022
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 Fri Dec 16 18:35:43 UTC 2022 , Edited by admin on Fri Dec 16 18:35:43 UTC 2022
Code System Code Type Description
ECHA (EC/EINECS)
262-450-6
Created by admin on Fri Dec 16 18:35:43 UTC 2022 , Edited by admin on Fri Dec 16 18:35:43 UTC 2022
PRIMARY
DAILYMED
9XE000OU9B
Created by admin on Fri Dec 16 18:35:43 UTC 2022 , Edited by admin on Fri Dec 16 18:35:43 UTC 2022
PRIMARY
EVMPD
SUB194326
Created by admin on Fri Dec 16 18:35:43 UTC 2022 , Edited by admin on Fri Dec 16 18:35:43 UTC 2022
PRIMARY
EPA CompTox
DTXSID40209671
Created by admin on Fri Dec 16 18:35:43 UTC 2022 , Edited by admin on Fri Dec 16 18:35:43 UTC 2022
PRIMARY
FDA UNII
9XE000OU9B
Created by admin on Fri Dec 16 18:35:43 UTC 2022 , Edited by admin on Fri Dec 16 18:35:43 UTC 2022
PRIMARY
RXCUI
259281
Created by admin on Fri Dec 16 18:35:43 UTC 2022 , Edited by admin on Fri Dec 16 18:35:43 UTC 2022
PRIMARY RxNorm
CAS
60834-30-2
Created by admin on Fri Dec 16 18:35:43 UTC 2022 , Edited by admin on Fri Dec 16 18:35:43 UTC 2022
PRIMARY
PUBCHEM
173769
Created by admin on Fri Dec 16 18:35:43 UTC 2022 , Edited by admin on Fri Dec 16 18:35:43 UTC 2022
PRIMARY
DRUG BANK
DBSALT001480
Created by admin on Fri Dec 16 18:35:43 UTC 2022 , Edited by admin on Fri Dec 16 18:35:43 UTC 2022
PRIMARY
ChEMBL
CHEMBL22
Created by admin on Fri Dec 16 18:35:43 UTC 2022 , Edited by admin on Fri Dec 16 18:35:43 UTC 2022
PRIMARY
WIKIPEDIA
Trimethoprim hydrochloride
Created by admin on Fri Dec 16 18:35:43 UTC 2022 , Edited by admin on Fri Dec 16 18:35:43 UTC 2022
PRIMARY
NCI_THESAURUS
C77554
Created by admin on Fri Dec 16 18:35:43 UTC 2022 , Edited by admin on Fri Dec 16 18:35:43 UTC 2022
PRIMARY
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