TRIMETHOPRIM HYDROCHLORIDE

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 Search

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

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf

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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Bacterial dihydrofolate reductase 5 Target ID: CHEMBL2364669 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19622858	Inhibitor 8146

Conditions

Condition	Modality	Targets	Highest Phase	Product
Urinary tract infections 202 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	Curative		Approved 8307	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

C_max

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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
10 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
56% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	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: https://pubmed.ncbi.nlm.nih.gov/3890282	unhealthy Health Status: unhealthy Condition: severe shigellosis Sources: https://pubmed.ncbi.nlm.nih.gov/3890282	Sources: https://pubmed.ncbi.nlm.nih.gov/3890282
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	Other AEs: Nausea, Vomiting... Other AEs: Nausea Vomiting Dizziness Headaches Confusion Bone marrow depression Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf

AEs

AE	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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1532 substrate 1670	substrate 985	inhibitor 1789

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 869 CYP2C19 1410 CYP1A2 1463 CYP2A6 670 CYP2E1 846 OCT2 630	CYP1A2 1013 CYP2A6 510 CYP2B6 648 CYP2C8 670

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2C8 923	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/\|https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1884466/ Page: 4.0	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
OCT2 631	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/19002438/	yes [IC50 1318 uM]
CYP1A2 1620	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition 250 uM]
CYP2C19 1484	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition 250 uM]
CYP2D6 1826	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition 250 uM]
CYP3A4 1857	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition 250 uM]
CYP2A6 702	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition <250 uM]
CYP2E1 929	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition <250 uM]

Drug as victim

Target	Modality	Activity
CYP1A2 1013	substrate 3264 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes
CYP2A6 510	substrate 3264 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes
CYP2B6 648	substrate 3264 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes
CYP2C8 670	substrate 3264 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes
CYP2C9 985	substrate 3264 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes
CYP3A4 1670	substrate 3264 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:45924	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:45924
ChemicalBook	CB2745185	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2745185
MolPort	MolPort-001-826-685	https://www.molport.com/shop/molecule-link/MolPort-001-826-685
Selleck Chemicals	trimethoprim	http://www.selleckchem.com/products/trimethoprim.html
ZINC	ZINC000006627681	http://zinc15.docking.org/substances/ZINC000006627681
eMolecules	27524526	https://www.emolecules.com/cgi-bin/more?vid=27524526
eMolecules	511466	https://www.emolecules.com/cgi-bin/more?vid=511466

PubMed

Title	Date	PubMed
Susceptibilities of Mycobacterium tuberculosis and Mycobacterium avium complex to lipophilic deazapteridine derivatives, inhibitors of dihydrofolate reductase.	1998 Dec	10052907
Synthesis and biological evaluation of 5-arylfuro[2,3-d]pyrimidines as novel dihydrofolate reductase inhibitors.	1999 Feb	10071850
Three-dimensional structure of M. tuberculosis dihydrofolate reductase reveals opportunities for the design of novel tuberculosis drugs.	2000 Jan 14	10623528
Prevalence of resistance to antimicrobials of Escherichia coli isolates from clinical sources at a private hospital in Trinidad.	2001 Apr	11427743
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	11584779
Antimicrobial resistance of Shigella spp isolated from diarrheal patients between 1989 and 1998 in Vietnam.	2001 Dec	12041563
Pneumocystis carinii pneumonitis in haemophagocytic lymphohistiocytosis.	2001 Dec	11853350
Empirical treatment of uncomplicated urinary tract infection by community pharmacist in the Eastern province of Saudi Arabia.	2001 Dec	11802186
Neonatal brucellosis and blood transfusion: case report and review of the literature.	2001 Dec	11732154
Public health lessons from a pilot programme to reduce mother-to-child transmission of HIV-1 in Khayelitsha.	2001 Jul	11544974
Etiologies of the urinary tract infections in a Yemeni City.	2001 Jul	11479641
Infectious complications in chronic lymphoid malignancy.	2001 Jun	12057123
Successful management of Brucella mellitensis endocarditis with combined medical and surgical approach.	2001 Jun	11404134
Patterns of antibiotic resistance, serotype distribution, and patient demographics of Streptococcus pneumoniae in Hong Kong.	2001 Mar-Apr	11173812
Changing pattern of biotypes, phage types & drug resistance of Salmonella typhi in Ludhiana during 1980-1999.	2001 May	11968951
Effect of early chemoprophylaxis with co-trimoxazole on nutritional status evolution in HIV-1-infected adults in Abidjan, Côte d'Ivoire.	2001 May 4	11399959
A common-source water-borne outbreak of multidrug-resistant typhoid fever in a rural Thai community.	2001 Nov	11853291
Co-trimoxazole compared with sulfadoxine-pyrimethamine in the treatment of uncomplicated malaria in Kenyan children.	2001 Nov-Dec	11816440
Epidemiological analysis of Salmonella enteritidis isolates in Singapore.	2001 Oct	11798253
Susceptibility patterns and serotypes of non-typhoidal salmonella in Trinidad.	2001 Oct	11744940
Occurrence of enteric redmouth disease in rainbow trout (Oncorhynchus mykiss) on farms in Croatia.	2002	12237969
Burkholderia pseudomallei: abscess in an unusual site.	2002 Apr-Jun	12215696
Clinical efficacy of co-trimoxazole versus amoxicillin twice daily for treatment of pneumonia: a randomised controlled clinical trial in Pakistan.	2002 Feb	11827905
Prophylactic antibiotic use in transurethral prostatic resection: a meta-analysis.	2002 Feb	11792921
Clinical and biological evolution of HIV-1 seroconverters in Abidjan, Côte d'Ivoire, 1997-2000.	2002 Feb 1	11832684
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	11754594
A double-hand transplant can be worth the effort!	2002 Jul 15	12134104
Prevalence of and resistance to anti-microbial drugs in selected microbial species isolated from bulk milk samples.	2002 Jun	12121041
In vitro activities of pentamidine, pyrimethamine, trimethoprim, and sulfonamides against Aspergillus species.	2002 Jun	12019133
The relation between sale of antimicrobial drugs and antibiotic resistance in uropathogens in general practice.	2002 Mar	12086284
Emergence of vancomycin-intermediate Staphylococcus aureus and S. sciuri, Greece.	2002 May	11996696
First characterization of a cluster of VanA-type glycopeptide-resistant Enterococcus faecium, Colombia.	2002 Sep	12194774

Patents

Sample Use Guides

In Vivo Use Guide

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

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

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