TRIMETHOPRIM LACTATE

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 Search

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	C14H18N4O3
Molecular Weight	290.3177
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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	( + / - )

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 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Urinary tract infections 205 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018679s044lbl.pdf	Curative		Approved 8429	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 1982

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 1587 substrate 1737	substrate 1037	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 911 CYP2C19 1478 CYP1A2 1524 CYP2A6 707 CYP2E1 882 OCT2 647	CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2C8 693

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2C8 965	inhibitor 3277 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 648	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19002438/	yes [IC50 1318 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition 250 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition 250 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition 250 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition 250 uM]
CYP2A6 739	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition <250 uM]
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12019187/ Page: 2,4	yes [Inhibition <250 uM]

Drug as victim

Target	Modality	Activity
CYP1A2 1054	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes
CYP2A6 543	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes
CYP2B6 664	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes
CYP2C8 693	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes
CYP2C9 1037	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067384/	yes
CYP3A4 1737	substrate 3367 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
Identification of Cryptosporidium parvum dihydrofolate reductase inhibitors by complementation in Saccharomyces cerevisiae.	2000 Apr	10722506
Three-dimensional structure of M. tuberculosis dihydrofolate reductase reveals opportunities for the design of novel tuberculosis drugs.	2000 Jan 14	10623528
The VISA/GISA problem: therapeutic implications.	2001	11688538
Clinical significance and impact on mortality of extended-spectrum beta lactamase-producing Enterobacteriaceae isolates in nosocomial bacteremia.	2001	11303808
Prevalence of resistance to antimicrobials of Escherichia coli isolates from clinical sources at a private hospital in Trinidad.	2001 Apr	11427743
[Whipple disease and non-Hodgkin lymphoma].	2001 Apr	11367979
Predominance of a methicillin-resistant Staphylococcus aureus clone susceptible to erythromycin and several other non-beta-lactam antibiotics in a Greek hospital.	2001 Aug	11481293
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
Gradient diffusion antibiotic susceptibility testing of potentially probiotic lactobacilli.	2001 Dec	11770631
Neonatal brucellosis and blood transfusion: case report and review of the literature.	2001 Dec	11732154
Bsoft: image and molecular processing in electron microscopy.	2001 Feb-Mar	11472087
[Antimicrobial therapy of urinary tract infections].	2001 Jan-Feb	11379193
Public health lessons from a pilot programme to reduce mother-to-child transmission of HIV-1 in Khayelitsha.	2001 Jul	11544974
Brucellosis in children of Dhofar Region, Oman.	2001 Jul	11479644
Association between tuberculosis and HIV disease progression in a high tuberculosis prevalence area.	2001 Mar	11326821
Co-trimoxazole and genital ulceration.	2001 Mar	11321861
Epidemiology of major respiratory pathogens.	2001 Nov	11936367
Synthesis of 2,4-diamino-6-(thioarylmethyl)pyrido[2,3-d]pyrimidines as dihydrofolate reductase inhibitors.	2001 Nov	11597474
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
Antibiotic use and resistance of Streptococcus pneumoniae in The Netherlands during the period 1994-1999.	2001 Sep	11533014
In vitro activity of novel fluoroquinolones against Streptococcus pneumoniae isolated from children with acute otitis media.	2001 Sep-Oct	11561138
Developing and testing instruments to measure client outcomes at the Comox Valley Nursing Center.	2001 Sep-Oct	11559416
Occurrence of enteric redmouth disease in rainbow trout (Oncorhynchus mykiss) on farms in Croatia.	2002	12237969
[General antibiotic therapy in acne].	2002 Apr 15	12053791
Burkholderia pseudomallei: abscess in an unusual site.	2002 Apr-Jun	12215696
Trimethoprim-induced aseptic meningitis in an adolescent male.	2002 Aug	12165625
Shigellosis linked to sex venues, Australia.	2002 Aug	12141976
Pneumocystis carinii: where are we now?	2002 Feb	11956498
Clinical efficacy of co-trimoxazole versus amoxicillin twice daily for treatment of pneumonia: a randomised controlled clinical trial in Pakistan.	2002 Feb	11827905
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
HIV-1/AIDS and maternal and child health in Africa.	2002 Jun 15	12086778
A disseminated multidrug-resistant clonal group of uropathogenic Escherichia coli in pyelonephritis.	2002 Jun 29	12103291
Modified antimicrobial disc susceptibility testing for nutritionally-variant streptococci.	2002 Mar	12118443
The relation between sale of antimicrobial drugs and antibiotic resistance in uropathogens in general practice.	2002 Mar	12086284
Q fever during pregnancy: diagnosis, treatment, and follow-up.	2002 Mar 25	11911725
Changes in Escherichia coli resistance to co-trimoxazole in tuberculosis patients and in relation to co-trimoxazole prophylaxis in Thyolo, Malawi.	2002 Mar-Apr	12055816
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 15 15:25:31 GMT 2023` Edited by `admin` on `Fri Dec 15 15:25:31 GMT 2023`
Record UNII	P3K8GP9FDQ
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

TRIMETHOPRIM LACTATE

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

SMS_ID

100000084666