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Identification
NameTrimethoprim
Accession NumberDB00440  (APRD00103)
TypeSmall Molecule
GroupsApproved
Description

A pyrimidine inhibitor of dihydrofolate reductase, it is an antibacterial related to pyrimethamine. The interference with folic acid metabolism may cause a depression of hematopoiesis. It is potentiated by sulfonamides and the trimethoprim-sulfamethoxazole combination is the form most often used. It is sometimes used alone as an antimalarial. Trimethoprim resistance has been reported. [PubChem]

Structure
Thumb
Synonyms
2,4-Diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine
5-[(3,4,5-Trimethoxyphenyl)methyl]-2,4-pyrimidinediamine
Proloprim
Trimethoprim
Triméthoprime
Trimethoprimum
Trimetoprima
Trimpex
External Identifiers
  • BW 56-72
  • Ro 6-2153-12 F
  • UNII-9XE000OU9B
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Primsolsolution50 mg/5mLoralAytu Bio Science, Inc.2015-09-15Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Primsolsolution50 mg/5mLoralFSC Laboratories, Inc2000-01-24Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Proloprim 200 Tab 200mgtablet200 mgoralGlaxosmithkline Inc1985-12-312004-08-05Canada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Proloprim Tab 100mgtablet100 mgoralGlaxosmithkline Inc1986-12-312003-10-28Canada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Trimethoprimtablet100 mg/1oralTeva Pharmaceuticals USA Inc1990-09-30Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Trimethoprim Tabletstablet200 mgoralAa Pharma Inc2001-07-30Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Trimethoprim Tabletstablet100 mgoralAa Pharma Inc2001-01-01Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Trimethoprimtablet100 mg/1oralWatson Laboratories, Inc.2010-04-04Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Trimethoprimtablet100 mg/1oralCarilion Materials Management2010-04-04Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Trimethoprimtablet100 mg/1oralPhysicians Total Care, Inc.2012-05-02Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Trimethoprimtablet100 mg/1oralREMEDYREPACK INC.2013-09-24Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Trimethoprimtablet100 mg/1oralAv Pak2013-07-31Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Trimethoprimtablet100 mg/1oralGAVIS Pharmaceuticals, LLC2011-06-24Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Trimethoprimtablet100 mg/1oralAv Kare, Inc.2013-05-06Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Trimethoprimtablet100 mg/1oralNovel Laboratories, Inc.2011-06-24Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Over the Counter ProductsNot Available
International Brands
NameCompany
AlprimAlphapharm
CatinKojar
EumiHwang's
InflamnilSwiss Pharm
LannacherRoot
LariagoIpca Laboratories
MeprimJohnson
MetipineKojar
MonotrimGlaxoSmithKline
MotrimLannacher
ProloprimGlaxoSmithKline
TrimpexNot Available
TriprimGlaxoSmithKline
Brand mixtures
NameLabellerIngredients
Apo Sulfatrim DS TabApotex Inc
Apo Sulfatrim PediatricApotex Inc
Apo Sulfatrim TabApotex Inc
Apo-sulfatrim Oral SusApotex Inc
BactrimAR Scientific, Inc.
Bactrim DSAR Scientific, Inc.
Bactrim DS Roche TabHoffmann La Roche Limited
Bactrim Roche InjHoffmann La Roche Limited
Bactrim Roche Suspension PaediatricHoffmann La Roche Limited
Bactrim Roche TabHoffmann La Roche Limited
Coptin Oral SuspensionAxcan Pharma Inc
Coptin TabPfizer Canada Inc
Nu-cotrimox Sus 40/8mg/mlNu Pharm Inc
Nu-cotrimox Tab 400/80mgNu Pharm Inc
Nu-cotrimox-DS Tab 800/160mgNu Pharm Inc
PMS-polytrimethoprimPharmascience Inc
Polymyxin B Sulfate and TrimethoprimSTAT RX LLC USA
Polymyxin B Sulfate and Trimethoprim SulfateMedsource Pharmaceuticals
PolytrimAllergan, Inc.
Polytrim Ophthalmic SolutionAllergan Inc
Protrin Df TabPro Doc Limitee
Protrin TabPro Doc Limitee
Riva-sep DSLaboratoire Riva Inc
Roubac Tab 160/800Rougier Pharma Division Of Ratiopharm Inc
Roubac Tab 80/400Rougier Pharma Division Of Ratiopharm Inc
Sandoz PolytrimethoprimSandoz Canada Incorporated
SeptraGlaxosmithkline Inc
Septra DS TabletsGlaxosmithkline Inc
Septra InjectionAspen Pharma Trading Limited
Septra Pediatric SuspensionGlaxosmithkline Inc
Sulfamethoxazole and TrimethoprimTeva Pharmaceuticals USA Inc
Sulfamethoxazole and Trimethoprim (double Strength)Teva Pharmaceuticals USA Inc
Sulfamethoxazole and Trimethoprim Double StrengthLake Erie Medical Dba Quality L Care Products Lc
Sulfamethoxazole and Trimethoprim DSApotheca Inc.
Sulfamethoxazole and Trimethoprim TabletsD.C. Labs Limited
SulfatrimSTI Pharma LLC
Teva-trimelTeva Canada Limited
Teva-trimel DSTeva Canada Limited
Trimethoprim Sulfate and Polymyxin B SulfateAkorn, Inc.
Trisulfa DS TabJaapharm Canada Inc.
Trisulfa S SuspensionJaapharm Canada Inc.
Trisulfa TabJaapharm Canada Inc.
Salts
Name/CASStructureProperties
Trimethoprim hydrochloride
ThumbNot applicableDBSALT001480
Trimethoprim sulfate
ThumbNot applicableDBSALT001471
Categories
UNIIAN164J8Y0X
CAS number738-70-5
WeightAverage: 290.3177
Monoisotopic: 290.137890462
Chemical FormulaC14H18N4O3
InChI KeyInChIKey=IEDVJHCEMCRBQM-UHFFFAOYSA-N
InChI
InChI=1S/C14H18N4O3/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)
IUPAC Name
5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidine-2,4-diamine
SMILES
COC1=CC(CC2=CN=C(N)N=C2N)=CC(OC)=C1OC
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as anisoles. These are organic compounds containing a methoxybenzene or a derivative thereof.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenol ethers
Direct ParentAnisoles
Alternative Parents
Substituents
  • Anisole
  • Aminopyrimidine
  • Alkyl aryl ether
  • Imidolactam
  • Pyrimidine
  • Primary aromatic amine
  • Heteroaromatic compound
  • Azacycle
  • Organoheterocyclic compound
  • Ether
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of urinary tract infections, uncomplicated pyelonephritis (with sulfamethoxazole) and mild acute prostatitis. May be used as pericoital (with sulfamethoxazole) or continuous prophylaxis in females with recurrent cystitis. May be used as an alternative to treat asymptomatic bacteriuria during pregnancy (only before the last 6 weeks of pregnancy). Other uses include: alternative agent in respiratory tract infections (otitis, sinusitus, bronchitis and pneumonia), treatment of Pneumocystis jirovecii pneumonia (acute or prophylaxis), Nocardia infections, and traveller's diarrhea.
PharmacodynamicsTrimethoprim is a pyrimidine analogue that disrupts folate synthesis, an essential part of the thymidine synthesis pathway. Inhibition of the enzyme starves the bacteria of nucleotides necessary for DNA replication.The drug, therefore, exhibits bactericidal activity.
Mechanism of actionTrimethoprim binds to dihydrofolate reductase and inhibits the reduction of dihydrofolic acid (DHF) to tetrahydrofolic acid (THF). THF is an essential precursor in the thymidine synthesis pathway and interference with this pathway inhibits bacterial DNA synthesis. Trimethoprim's affinity for bacterial dihydrofolate reductase is several thousand times greater than its affinity for human dihydrofolate reductase. Sulfamethoxazole inhibits dihydrofolate synthetase (aka dihydropteroate synthetase), an enzyme involved further upstream in the same pathway. Trimethoprim and sulfamethoxazole are commonly used in combination due to their synergistic effects. This drug combination also reduces the development of resistance that is seen when either drug is used alone.
AbsorptionReadily and almost completely absorbed in the GI tract with peak serum concentrations attained 1-4 hours after oral administration. Widely distributed to tissues and fluids including kidney, lung, seminal fluid, aqueous humour, middle ear fluid, sputum, vaginal secretions, bile, bone and CSF.
Volume of distributionNot Available
Protein binding42-46% bound to plasma proteins
Metabolism

Hepatic metabolism to oxide and hydroxylated metabolites.

Route of eliminationTen to twenty percent of trimethoprim is metabolized, primarily in the liver; the remainder is excreted unchanged in the urine. After oral administration, 50% to 60% of trimethoprim is excreted in the urine within 24 hours, approximately 80% of this being unmetabolized trimethoprim. Trimethoprim also passes the placental barrier and is excreted in human milk.
Half life8-11 hours in adults with normal renal function
ClearanceNot Available
ToxicityLD50=4850 (orally in mice)
Affected organisms
  • Gram negative and gram positive bacteria
  • Listeria monocytogenes
  • Escherichia coli
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.994
Blood Brain Barrier+0.9381
Caco-2 permeable+0.8867
P-glycoprotein substrateNon-substrate0.5845
P-glycoprotein inhibitor INon-inhibitor0.8631
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterNon-inhibitor0.8531
CYP450 2C9 substrateNon-substrate0.8799
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.5732
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8467
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5
Ames testNon AMES toxic0.8227
CarcinogenicityNon-carcinogens0.9369
BiodegradationNot ready biodegradable0.9949
Rat acute toxicity1.7701 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9394
hERG inhibition (predictor II)Non-inhibitor0.8734
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Monarch pharmaceuticals inc
  • Mutual pharmaceutical co inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
  • Hoffmann la roche inc
  • Fsc laboratories inc
Packagers
Dosage forms
FormRouteStrength
Liquidintravenous
Liquidophthalmic
Solutionophthalmic
Solution/ dropsophthalmic
Solutionoral50 mg/5mL
Solutionintravenous
Injection, solution, concentrateintravenous
Suspensionoral
Tabletoral
Tabletoral100 mg/1
Tabletoral100 mg
Tabletoral200 mg
Prices
Unit descriptionCostUnit
Bactrim ds tablet5.53USD tablet
Bactrim DS 800-160 mg tablet3.0USD tablet
Septra DS 800-160 mg tablet2.43USD tablet
Septra ds tablet2.33USD tablet
Trimethoprim powder1.79USD g
Bactrim 400-80 mg tablet1.63USD tablet
Septra 80-400 tablet1.49USD tablet
Sulfamethoxazole-tmp ds tablet1.44USD tablet
Sulfamethoxazole-tmp vial0.84USD ml
Trimethoprim 100 mg tablet0.7USD tablet
Sulfamethoxazole-Trimethoprim 400-80 mg tablet0.69USD tablet
Apo-Trimethoprim 200 mg Tablet0.55USD tablet
Primsol 50 mg/5 ml oral soln0.39USD ml
Apo-Trimethoprim 100 mg Tablet0.27USD tablet
Sulfamethoxazole-tmp ss tablet0.17USD tablet
Sulfamethoxazole-Trimethoprim 200-40 mg/5ml Suspension0.13USD ml
Sulfatrim 200-40 mg/5ml Suspension0.13USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States57634491996-08-072016-08-07
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point199-203 °CPhysProp
water solubility400 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP0.91HANSCH,C ET AL. (1995)
logS-2.86ADME Research, USCD
pKa7.12 (at 20 °C)PERRIN,DD (1972)
Predicted Properties
PropertyValueSource
Water Solubility0.615 mg/mLALOGPS
logP1.26ALOGPS
logP1.28ChemAxon
logS-2.7ALOGPS
pKa (Strongest Acidic)17.33ChemAxon
pKa (Strongest Basic)7.16ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area105.51 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity81.51 m3·mol-1ChemAxon
Polarizability29.71 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Yasushi Takagishi, Kiichiro Ohsuga, Sadao Ohama, “Suppository containing sulfamethoxazole/trimethoprim complex and process for preparing the same.” U.S. Patent US4461765, issued December, 1975.

US4461765
General References
  1. Brumfitt W, Hamilton-Miller JM: Reassessment of the rationale for the combinations of sulphonamides with diaminopyrimidines. J Chemother. 1993 Dec;5(6):465-9. Pubmed
  2. Brumfitt W, Hamilton-Miller JM: Limitations of and indications for the use of co-trimoxazole. J Chemother. 1994 Feb;6(1):3-11. Pubmed
  3. Bean DC, Livermore DM, Papa I, Hall LM: Resistance among Escherichia coli to sulphonamides and other antimicrobials now little used in man. J Antimicrob Chemother. 2005 Nov;56(5):962-4. Epub 2005 Sep 8. Pubmed
  4. Felmingham D, Reinert RR, Hirakata Y, Rodloff A: Increasing prevalence of antimicrobial resistance among isolates of Streptococcus pneumoniae from the PROTEKT surveillance study, and compatative in vitro activity of the ketolide, telithromycin. J Antimicrob Chemother. 2002 Sep;50 Suppl S1:25-37. Pubmed
  5. Johnson JR, Manges AR, O’Bryan TT, Riley LW: A disseminated multidrug-resistant clonal group of uropathogenic Escherichia coli in pyelonephritis. Lancet. 2002 Jun 29;359(9325):2249-51. Pubmed
External Links
ATC CodesJ01EA01
AHFS Codes
  • 08:36.00
PDB EntriesNot Available
FDA labelDownload (98.5 KB)
MSDSDownload (74.3 KB)
Interactions
Drug Interactions
Drug
AcetohexamideAcetohexamide may increase the hypoglycemic activities of Trimethoprim.
Acetylsalicylic acidAcetylsalicylic acid may increase the hypoglycemic activities of Trimethoprim.
AlogliptinAlogliptin may increase the hypoglycemic activities of Trimethoprim.
AmantadineThe risk or severity of adverse effects can be increased when Trimethoprim is combined with Amantadine.
AmiodaroneThe metabolism of Amiodarone can be decreased when combined with Trimethoprim.
AmodiaquineTrimethoprim may increase the neutropenic activities of Amodiaquine.
AzathioprineTrimethoprim may increase the myelosuppressive activities of Azathioprine.
Azilsartan medoxomilTrimethoprim may increase the hyperkalemic activities of Azilsartan medoxomil.
BenazeprilTrimethoprim may increase the hyperkalemic activities of Benazepril.
BexaroteneThe serum concentration of Trimethoprim can be decreased when it is combined with Bexarotene.
BosentanThe serum concentration of Trimethoprim can be decreased when it is combined with Bosentan.
CanagliflozinCanagliflozin may increase the hypoglycemic activities of Trimethoprim.
CandesartanTrimethoprim may increase the hyperkalemic activities of Candesartan.
CaptoprilTrimethoprim may increase the hyperkalemic activities of Captopril.
CarvedilolThe serum concentration of Carvedilol can be increased when it is combined with Trimethoprim.
CeritinibThe serum concentration of Trimethoprim can be increased when it is combined with Ceritinib.
ChlorpropamideTrimethoprim may increase the hypoglycemic activities of Chlorpropamide.
CilazaprilTrimethoprim may increase the hyperkalemic activities of Cilazapril.
CitalopramTrimethoprim may increase the QTc-prolonging activities of Citalopram.
CyclosporineTrimethoprim may increase the nephrotoxic activities of Cyclosporine.
DabrafenibThe serum concentration of Trimethoprim can be decreased when it is combined with Dabrafenib.
DapsoneThe serum concentration of Dapsone can be increased when it is combined with Trimethoprim.
DeferasiroxThe serum concentration of Trimethoprim can be decreased when it is combined with Deferasirox.
DexketoprofenThe risk or severity of adverse effects can be increased when Dexketoprofen is combined with Trimethoprim.
DicoumarolTrimethoprim may increase the anticoagulant activities of Dicoumarol.
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Trimethoprim.
DihydrotestosteroneDihydrotestosterone may increase the hypoglycemic activities of Trimethoprim.
DofetilideTrimethoprim may decrease the excretion rate of Dofetilide which could result in a lower serum level and potentially a reduction in efficacy.
DronabinolThe serum concentration of Dronabinol can be increased when it is combined with Trimethoprim.
EnalaprilTrimethoprim may increase the hyperkalemic activities of Enalapril.
EnalaprilatTrimethoprim may increase the hyperkalemic activities of Enalaprilat.
EnzalutamideThe metabolism of Enzalutamide can be decreased when combined with Trimethoprim.
EplerenoneTrimethoprim may increase the hyperkalemic activities of Eplerenone.
EprosartanTrimethoprim may increase the hyperkalemic activities of Eprosartan.
FloxuridineThe metabolism of Trimethoprim can be decreased when combined with Floxuridine.
FluconazoleThe metabolism of Trimethoprim can be decreased when combined with Fluconazole.
FosinoprilTrimethoprim may increase the hyperkalemic activities of Fosinopril.
FosphenytoinThe serum concentration of Trimethoprim can be decreased when it is combined with Fosphenytoin.
GliclazideGliclazide may increase the hypoglycemic activities of Trimethoprim.
GlimepirideGlimepiride may increase the hypoglycemic activities of Trimethoprim.
GliquidoneGliquidone may increase the hypoglycemic activities of Trimethoprim.
GlyburideGlyburide may increase the hypoglycemic activities of Trimethoprim.
GoserelinTrimethoprim may increase the QTc-prolonging activities of Goserelin.
HexamethylenetetramineThe risk or severity of adverse effects can be increased when Hexamethylenetetramine is combined with Trimethoprim.
Insulin AspartInsulin Aspart may increase the hypoglycemic activities of Trimethoprim.
Insulin DetemirInsulin Detemir may increase the hypoglycemic activities of Trimethoprim.
Insulin GlargineInsulin Glargine may increase the hypoglycemic activities of Trimethoprim.
Insulin GlulisineInsulin Glulisine may increase the hypoglycemic activities of Trimethoprim.
Insulin LisproInsulin Lispro may increase the hypoglycemic activities of Trimethoprim.
Insulin RegularInsulin Regular may increase the hypoglycemic activities of Trimethoprim.
Insulin, isophaneInsulin, isophane may increase the hypoglycemic activities of Trimethoprim.
IrbesartanTrimethoprim may increase the hyperkalemic activities of Irbesartan.
LamivudineTrimethoprim may decrease the excretion rate of Lamivudine which could result in a lower serum level and potentially a reduction in efficacy.
LeuprolideTrimethoprim may increase the QTc-prolonging activities of Leuprolide.
LinagliptinLinagliptin may increase the hypoglycemic activities of Trimethoprim.
LisinoprilTrimethoprim may increase the hyperkalemic activities of Lisinopril.
LosartanTrimethoprim may increase the hyperkalemic activities of Losartan.
MemantineThe risk or severity of adverse effects can be increased when Trimethoprim is combined with Memantine.
MercaptopurineTrimethoprim may increase the myelosuppressive activities of Mercaptopurine.
MetforminThe serum concentration of Metformin can be increased when it is combined with Trimethoprim.
MethotrexateThe risk or severity of adverse effects can be increased when Trimethoprim is combined with Methotrexate.
MifepristoneThe serum concentration of Trimethoprim can be increased when it is combined with Mifepristone.
MitotaneThe serum concentration of Trimethoprim can be decreased when it is combined with Mitotane.
MoexiprilTrimethoprim may increase the hyperkalemic activities of Moexipril.
OlmesartanTrimethoprim may increase the hyperkalemic activities of Olmesartan.
OxandroloneOxandrolone may increase the hypoglycemic activities of Trimethoprim.
PaclitaxelThe metabolism of Paclitaxel can be decreased when combined with Trimethoprim.
ParoxetineParoxetine may increase the hypoglycemic activities of Trimethoprim.
PerindoprilTrimethoprim may increase the hyperkalemic activities of Perindopril.
PhenelzinePhenelzine may increase the hypoglycemic activities of Trimethoprim.
PhenytoinThe serum concentration of Phenytoin can be increased when it is combined with Trimethoprim.
PioglitazoneThe metabolism of Pioglitazone can be decreased when combined with Trimethoprim.
PralatrexateThe serum concentration of Pralatrexate can be increased when it is combined with Trimethoprim.
ProcainamideThe serum concentration of the active metabolites of Procainamide can be increased when Procainamide is used in combination with Trimethoprim.
QuinaprilTrimethoprim may increase the hyperkalemic activities of Quinapril.
RamiprilTrimethoprim may increase the hyperkalemic activities of Ramipril.
RepaglinideThe metabolism of Repaglinide can be decreased when combined with Trimethoprim.
RosiglitazoneThe metabolism of Rosiglitazone can be decreased when combined with Trimethoprim.
Salicylate-sodiumSalicylate-sodium may increase the hypoglycemic activities of Trimethoprim.
SaxagliptinSaxagliptin may increase the hypoglycemic activities of Trimethoprim.
SecobarbitalThe metabolism of Trimethoprim can be increased when combined with Secobarbital.
SildenafilThe metabolism of Sildenafil can be decreased when combined with Trimethoprim.
SiltuximabThe serum concentration of Trimethoprim can be decreased when it is combined with Siltuximab.
Sodium picosulfateThe therapeutic efficacy of Sodium picosulfate can be decreased when used in combination with Trimethoprim.
SparfloxacinSparfloxacin may increase the hypoglycemic activities of Trimethoprim.
SpironolactoneTrimethoprim may increase the hyperkalemic activities of Spironolactone.
St. John's WortThe serum concentration of Trimethoprim can be decreased when it is combined with St. John's Wort.
SulfisoxazoleThe metabolism of Trimethoprim can be decreased when combined with Sulfisoxazole.
TelmisartanTrimethoprim may increase the hyperkalemic activities of Telmisartan.
TestosteroneTestosterone may increase the hypoglycemic activities of Trimethoprim.
TocilizumabThe serum concentration of Trimethoprim can be decreased when it is combined with Tocilizumab.
TolbutamideTolbutamide may increase the hypoglycemic activities of Trimethoprim.
TorasemideThe metabolism of Torasemide can be decreased when combined with Trimethoprim.
TrandolaprilTrimethoprim may increase the hyperkalemic activities of Trandolapril.
TranylcypromineTranylcypromine may increase the hypoglycemic activities of Trimethoprim.
TretinoinThe metabolism of Tretinoin can be decreased when combined with Trimethoprim.
TroglitazoneThe metabolism of Troglitazone can be decreased when combined with Trimethoprim.
ValsartanTrimethoprim may increase the hyperkalemic activities of Valsartan.
VareniclineThe serum concentration of Varenicline can be increased when it is combined with Trimethoprim.
VildagliptinVildagliptin may increase the hypoglycemic activities of Trimethoprim.
Food Interactions
  • Do not take calcium, aluminium, magnesium or iron supplements within 2 hours of taking this medication.
  • Take on empty stomach: 1 hour before or 2 hours after meals.
  • Take with a full glass of water.

Targets

1. Thymidylate synthase

Kind: Protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Thymidylate synthase P04818 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Gamarro F, Yu PL, Zhao J, Edman U, Greene PJ, Santi D: Trypanosoma brucei dihydrofolate reductase-thymidylate synthase: gene isolation and expression and characterization of the enzyme. Mol Biochem Parasitol. 1995 Jun;72(1-2):11-22. Pubmed
  4. Rosowsky A, Papoulis AT, Forsch RA, Queener SF: Synthesis and antiparasitic and antitumor activity of 2, 4-diamino-6-(arylmethyl)-5,6,7,8-tetrahydroquinazoline analogues of piritrexim. J Med Chem. 1999 Mar 25;42(6):1007-17. Pubmed
  5. Reche P, Arrebola R, Santi DV, Gonzalez-Pacanowska D, Ruiz-Perez LM: Expression and characterization of the Trypanosoma cruzi dihydrofolate reductase domain. Mol Biochem Parasitol. 1996 Feb-Mar;76(1-2):175-85. Pubmed
  6. Oefner C, Parisi S, Schulz H, Lociuro S, Dale GE: Inhibitory properties and X-ray crystallographic study of the binding of AR-101, AR-102 and iclaprim in ternary complexes with NADPH and dihydrofolate reductase from Staphylococcus aureus. Acta Crystallogr D Biol Crystallogr. 2009 Aug;65(Pt 8):751-7. Epub 2009 Jul 10. Pubmed
  7. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

2. Dihydrofolate reductase

Kind: Protein

Organism: Human

Pharmacological action: no

Actions: inhibitor

Components

Name UniProt ID Details
Dihydrofolate reductase P00374 Details

References:

  1. Laskowska E, Kuczynska-Wisnik D, Bak M, Lipinska B: Trimethoprim induces heat shock proteins and protein aggregation in E. coli cells. Curr Microbiol. 2003 Oct;47(4):286-9. Pubmed
  2. Floris-Moore MA, Amodio-Groton MI, Catalano MT: Adverse reactions to trimethoprim/sulfamethoxazole in AIDS. Ann Pharmacother. 2003 Dec;37(12):1810-3. Pubmed
  3. Rosowsky A, Fu H, Chan DC, Queener SF: Synthesis of 2,4-diamino-6-[2’-O-(omega-carboxyalkyl)oxydibenz[b,f]azepin-5-yl]methylpt eridines as potent and selective inhibitors of Pneumocystis carinii, Toxoplasma gondii, and Mycobacterium avium dihydrofolate reductase. J Med Chem. 2004 May 6;47(10):2475-85. Pubmed
  4. Nahimana A, Rabodonirina M, Bille J, Francioli P, Hauser PM: Mutations of Pneumocystis jirovecii dihydrofolate reductase associated with failure of prophylaxis. Antimicrob Agents Chemother. 2004 Nov;48(11):4301-5. Pubmed
  5. Barrow EW, Bourne PC, Barrow WW: Functional cloning of Bacillus anthracis dihydrofolate reductase and confirmation of natural resistance to trimethoprim. Antimicrob Agents Chemother. 2004 Dec;48(12):4643-9. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Enzymes

1. Cytochrome P450 2C8

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2C9

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 3A4

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Transporters

1. Multidrug resistance protein 1

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor inducer

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Romiti N, Tramonti G, Chieli E: Influence of different chemicals on MDR-1 P-glycoprotein expression and activity in the HK-2 proximal tubular cell line. Toxicol Appl Pharmacol. 2002 Sep 1;183(2):83-91. Pubmed
  2. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on November 30, 2015 12:10