Abacin;Abaprim;Alprim;Apo-Sulfatrim;Bactin;Bactramin;Bactrim;Bactrim DS;Bactrim Pediatric;Baktar;Chemotrim;Co-Trimoxazole;Comox;Cotrim;Cotrim D.S.;Drylin;Eusaprim;Fectrim;Gantaprim;Gantrim;Idotrim;Imexim;Instalac;Ipral;Kepinol;Laratrim;Lidaprim;Methoprim;Microtrim;Monoprim;Monotrim;Monotrimin;Nopil;Oraprim;Priloprim;Primosept;Primsol;Proloprim;Septra;Septra DS;Septra Grape;Septrin;Sigaprim;Sulfamethoprim;Sulfamethoprim-DS;Sulfamethoxazole & Trimethoprim;Sulfatrim;Sulfatrim Pediatric;Sulfatrim-DS;Sulfatrim-SS;Sulfotrim;Sulmeprim;Sulmeprim Pediatric;Sulprim;Sumetrolim;Supracombin;Suprim;Syraprim;Teleprim;Thiocuran;Tiempe;Tmp-Ratiopharm;Trigonyl;Trimanyl;Trimesulf;Trimeth/Sulfa;Trimethioprim;Trimethopriom;Trimetoprim;Trimexazole;Trimogal;Trimopan;Trimpex;Trimpex 200;Triprim;Unitrim;Uretrim;Uro-Septra;Uroplus;Uroplus DS;Uroplus SS;Wellcoprim;

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]

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Synthesis Reference

Not Available

General Reference

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 Brumfitt W, Hamilton-Miller JM: Limitations of and indications for the use of co-trimoxazole. J Chemother. 1994 Feb;6(1):3-11. Pubmed 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 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 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

Type	small molecule

Classes

Phenols and Derivatives Ethers Catechols Anisoles Phenyl Esters

Substructures

Phenols and Derivatives Aliphatic and Aryl Amines Ethers Benzene and Derivatives Pyrimidines and Derivatives Catechols Heterocyclic compounds Aromatic compounds Anisoles Cyanamides Phenyl Esters

antibacterials 抗细菌;

Indication	For 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.
Pharmacodynamics	Trimethoprim 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 action	Trimethoprim 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.
Absorption	Readily 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 distribution	Not Available
Protein binding	42-46% bound to plasma proteins
Metabolism	Hepatic metabolism to oxide and hydroxylated metabolites.
Route of elimination	Ten 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 life	8-11 hours in adults with normal renal function
Clearance	Not Available
Toxicity	LD50=4850 (orally in mice)
Affected organisms	Gram negative and gram positive bacteria
Pathways	Not Available

Properties
State	solid
Experimental Properties	Property Value Source melting point 199-203 °C PhysProp water solubility 400 mg/L (at 25 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992) logP 0.91 HANSCH,C ET AL. (1995) logS -2.86 ADME Research, USCD pKa 7.12 (at 20 °C) PERRIN,DD (1972)
Predicted Properties	Property Value Source water solubility 6.15e-01 g/l ALOGPS logP 1.26 ALOGPS logP 1.28 ChemAxon logS -2.7 ALOGPS pKa (strongest acidic) 17.33 ChemAxon pKa (strongest basic) 7.16 ChemAxon physiological charge 1 ChemAxon hydrogen acceptor count 7 ChemAxon hydrogen donor count 2 ChemAxon polar surface area 105.51 ChemAxon rotatable bond count 5 ChemAxon refractivity 81.51 ChemAxon polarizability 29.71 ChemAxon

Drug	Interaction
Capecitabine	The strong CYP2C9 inhibitor, Capecitabine, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Capecitabine is initiated, discontinued or dose changed.
Dapsone	Increased toxicity of both products
Delavirdine	The strong CYP2C9 inhibitor, Delavirdine, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Delavirdine is initiated, discontinued or dose changed.
Dofetilide	Trimethoprim may significantly reduced the clearance of Dofetilide. Trimethoprim is a cation transport inhibitor and may interfere with renal excretion of Dofetilide. Concomitant use is contraindicated.
Floxuridine	The strong CYP2C9 inhibitor, Floxuridine, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Floxuridine is initiated, discontinued or dose changed.
Fluconazole	The strong CYP2C9 inhibitor, Fluconazole, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Fluconazole is initiated, discontinued or dose changed.
Fluorouracil	The strong CYP2C9 inhibitor, Fluorouracil, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Fluorouracil is initiated, discontinued or dose changed.
Flurbiprofen	The strong CYP2C9 inhibitor, Flurbiprofen, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Flurbiprofen is initiated, discontinued or dose changed.
Fosphenytoin	Trimethoprim increases the effect of hydantoin
Gemfibrozil	The strong CYP2C9 inhibitor, Gemfibrozil, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Gemfibrozil is initiated, discontinued or dose changed.
Ibuprofen	The strong CYP2C9 inhibitor, Ibuprofen, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Ibuprofen is initiated, discontinued or dose changed.
Indomethacin	The strong CYP2C9 inhibitor, Indomethacine, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Indomethacine is initiated, discontinued or dose changed.
Ketoconazole	The strong CYP2C9 inhibitor, Ketoconazole, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Ketoconazole is initiated, discontinued or dose changed.
Leucovorin	The efficacy of Trimethoprim may be reduced by Leucovorin (folinic acid). The antibiotic, Trimethoprim, acts by blocking bacterial folic acid metabolism. Leucovorin may reduce the efficacy of Trimethoprim by providing an alternate source of folic acid. The therapeutic effect of Trimethoprim should be closely monitored.
Mefenamic acid	The strong CYP2C9 inhibitor, Mefenamic acid, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Mefenamic acid is initiated, discontinued or dose changed.
Methotrexate	Trimethoprim may increase the adverse/toxic effects of Methotrexate (e.g. bone marrow suppression). Concomitant use should be avoided or closely monitored for Methotrexate toxicity.
Miconazole	The strong CYP2C9 inhibitor, Miconazole, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Miconazole is initiated, discontinued or dose changed.
Nicardipine	The strong CYP2C9 inhibitor, Nicardipine, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Nicardipine is initiated, discontinued or dose changed.
Phenytoin	Trimethoprim increases the effect of hydantoin
Piroxicam	The strong CYP2C9 inhibitor, Piroxicam, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Piroxicam is initiated, discontinued or dose changed.
Procainamide	Trimethoprim may reduce the clearance of Procainamide. Alternative treatments should be considered. If Trimethoprim is initiated or the dose is increased, monitor for increased toxicity of Procainamide (e.g. QTc intervals, EKG, serum drug concentrations). If Trimethoprim is discontinued or the dose decreased, monitor for reduced effects of Procainamide.
Rifampin	Rifampin decreases the effect of trimethoprim
Sitaxentan	The strong CYP2C9 inhibitor, Sitaxsentan, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Sitaxsentan is initiated, discontinued or dose changed.
Sulfadiazine	The strong CYP2C9 inhibitor, Sulfadiazine, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Sulfadiazine is initiated, discontinued or dose changed.
Sulfisoxazole	The strong CYP2C9 inhibitor, Sulfisoxazole, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Sulfisoxazole is initiated, discontinued or dose changed.
Tobramycin	Increased risk of nephrotoxicity
Tolbutamide	The strong CYP2C9 inhibitor, Tolbutamide, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Tolbutamide is initiated, discontinued or dose changed.
Trandolapril	Increased risk of hyperkalemia. Monitor serum potassium levels.
Tretinoin	The moderate CYP2C8 inhibitor, Trimethoprim, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Trimethoprim is initiated, discontinued to dose changed.

• 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.