QuickView for Trimethoprim (compound)

Summary
General Info

PubChem

PubChem Compound 173769

Name:	Trimethoprim
PubChem Compound ID:	173769
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.
Molecular formula:	C₁₄H₁₉ClN₄O₃
Molecular weight:	326.779 g/mol
Synonyms:	60834-30-2; 5-((3,4,5-Trimethoxyphenyl)methyl)pyrimidine-2,4-diamine hydrochloride; EINECS 262-450-6

DrugBank

Identification

Name:	Trimethoprim
Name (isomeric):	DB00440
Drug Type:	small molecule
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.
Brand:	Abaprim, Sigaprim, Kepinol, Trimethopriom, Trimexazole, Trimethioprim, Uretrim, Teleprim, Fectrim, Uroplus SS, Sulfatrim-SS, Thiocuran, Sulmeprim Pediatric, Bactrim Pediatric, Septra DS, Instalac, Lidaprim, Primosept, Sulprim, Proloprim, Unitrim, Trimeth/Sulfa, Sulfamethoprim-DS, Sulfamethoxazole & Trimethoprim, Uroplus DS, Trimopan, Suprim, Abacin, Supracombin, Microtrim, Trimpex, Trimesulf, Drylin, Primsol, Bactin, Uroplus, Monoprim, Apo-Sulfatrim, Oraprim, Trimetoprim, Alprim, Methoprim, Sulfatrim Pediatric, Co-Trimoxazole, Priloprim, Sulfotrim, Sulmeprim, Trimanyl, Trigonyl, Cotrim, Bactrim DS, Monotrim, Sulfatrim, Trimpex 200, Baktar, Cotrim D.S., Laratrim, Sumetrolim, Chemotrim, Gantrim, Comox, Imexim, Sulfatrim-DS, Trimogal, Gantaprim, Monotrimin, Syraprim, Ipral, Septra, Sulfamethoprim, Bactrim, Septrin, Septra Grape, Eusaprim, Wellcoprim, Uro-Septra, Idotrim, Nopil, Triprim, Tmp-Ratiopharm, Tiempe, Bactramin
Category:	Antimalarials, Anti-Infective Agents, Urinary, Folic Acid Antagonists, Anti-Infectives
CAS number:	738-70-5

Pharmacology

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.
Pharmacology:	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 tim... show more » 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. show less «
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.
Protein binding:	42-46% bound to plasma proteins
Biotransformation:	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
Toxicity:	LD₅₀=4850 (orally in mice)
Affected organisms:	Gram negative and gram positive bacteria

Interactions

Food interaction:

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.

Drug interaction:

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.
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.
Fosphenytoin	Trimethoprim increases the effect of hydantoin
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.
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.

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.
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.
Fosphenytoin	Trimethoprim increases the effect of hydantoin
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.
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.
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.
Rifampin	Rifampin decreases the effect of trimethoprim
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.
Trandolapril	Increased risk of hyperkalemia. Monitor serum potassium levels.
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.
Phenytoin	Trimethoprim increases the effect of hydantoin
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.
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.
Tobramycin	Increased risk of nephrotoxicity
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

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Targets

Thymidylate synthase

Dihydrofolate reductase

Enzymes

Cytochrome P450 2C9

Cytochrome P450 3A4

Cytochrome P450 2C8

Transporters

Multidrug resistance protein 1