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Trimethoprim

January 30, 2023

Not to be confused with Thymidine monophosphate.

Trimethoprim (TMP) is an antibiotic used mainly in the treatment of bladder infections.[1] Other uses include for middle ear infections and travelers' diarrhea.[1] With sulfamethoxazole or dapsone it may be used for Pneumocystis pneumonia in people with HIV/AIDS.[1][2] It is taken by mouth.[1]

Trimethoprim
Clinical data
Pronunciation/traɪˈmɛθəprɪm/
Trade namesProloprim, Monotrim, Triprim, others
AHFS/Drugs.comMonograph
MedlinePlusa684025
License data
  • US FDA: Trimethoprim
Pregnancy
category
  • AU: B3
Routes of
administration		Oral
Drug classDiaminopyrimidines
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability90–100%
Protein binding44%
Metabolismhepatic
Elimination half-life8–12 hours
ExcretionUrine (50–60%), faeces (4%)
Identifiers
  • 5-(3,4,5-Trimethoxybenzyl)pyrimidine-2,4-diamine
CAS Number
  • 738-70-5 Y
PubChem CID
  • 5578
DrugBank
  • DB00440 Y
ChemSpider
  • 5376 Y
UNII
  • AN164J8Y0X
KEGG
  • D00145 Y
ChEBI
  • CHEBI:45924 Y
ChEMBL
  • ChEMBL22 Y
PDB ligand
  • TOP (PDBe, RCSB PDB)
CompTox Dashboard (EPA)
  • DTXSID3023712
ECHA InfoCard100.010.915
Chemical and physical data
FormulaC14H18N4O3
Molar mass290.323 g·mol−1
3D model (JSmol)
  • Interactive image
  • Nc1nc(N)ncc1Cc(cc2OC)cc(OC)c2OC
  • 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) Y
  • Key:IEDVJHCEMCRBQM-UHFFFAOYSA-N Y
  (verify)

Common side effects include nausea, changes in taste, and rash.[1] Rarely it may result in blood problems such as not enough platelets or white blood cells.[1] Trimethoprim may cause sun sensitivity.[1] There is evidence of potential harm during pregnancy in some animals but not humans.[3] It works by blocking folate metabolism via dihydrofolate reductase in some bacteria which results in their death.[1]

Trimethoprim was first used in 1962.[4] It is on the World Health Organization's List of Essential Medicines.[5] It is available as a generic medication.[6]

Medical uses

It is primarily used in the treatment of urinary tract infections, although it may be used against any susceptible aerobic bacterial species.[7] It may also be used to treat and prevent Pneumocystis jirovecii pneumonia.[7] It is generally not recommended for the treatment of anaerobic infections such as Clostridium difficile colitis (the leading cause of antibiotic-induced diarrhea).[7] Trimethoprim has been used in trials to treat retinitis.[8]

Resistance to trimethoprim is increasing, but it is still a first line antibiotic in many countries.[9]

Spectrum of susceptibility

Cultures and susceptibility tests should be done to make sure bacteria are treated by trimethoprim.[10][11]

Side effects

Common

  • Nauseas
  • Change in taste
  • Vomiting
  • Diarrhea
  • Rashes
  • Sun sensitivity
  • Itchiness[12][13]

Rare

Contraindications

Pregnancy

Based on the studies that show that trimethoprim crosses the placenta and can affect folate metabolism, there has been growing evidence of the risk of structural birth defects associated with trimethoprim, especially during the first trimester of pregnancy.[19] It may be involved in a reaction similar to disulfiram when alcohol is consumed after it is used, in particular when used in combination with sulfamethoxazole.[20][21] The trophoblasts in the early fetus are sensitive to changes in the folate cycle. A recent study has found a doubling in the risk of miscarriage in women exposed to trimethoprim in the early pregnancy.[22]

Mechanism of action

 
Staphylococcus aureus DHFR in complex with NADPH and trimethoprim PDB entry 2W9G [23]

Trimethoprim binds to dihydrofolate reductase and inhibits the reduction of dihydrofolic acid (DHF) to tetrahydrofolic acid (THF).[24] THF is an essential precursor in the thymidine synthesis pathway and interference with this pathway inhibits bacterial DNA synthesis.[24] Trimethoprim's inhibitory activity for bacterial dihydrofolate reductase is sixty thousand times greater than for human dihydrofolate reductase.[25] Sulfamethoxazole inhibits dihydropteroate synthase, an enzyme involved further upstream in the same pathway.[24] Trimethoprim and sulfamethoxazole are commonly used in combination due to possible synergistic effects, and reduced development of resistance.[24] This benefit has been questioned.[26]

 
Tetrahydrofolate synthesis pathway

History

Trimethoprim was first used in 1962.[4] In 1972, it was used as a prophylactic treatment for urinary tract infections in Finland.[4]

Its name is derived from trimethyloxy-pyrimidine.

See also

References

  1. ^ a b c d e f g h "Trimethoprim". The American Society of Health-System Pharmacists. from the original on 2015-09-24. Retrieved Aug 1, 2015.
  2. ^ Masur, H; Brooks, JT; Benson, CA; Holmes, KK; Pau, AK; Kaplan, JE; National Institutes of, Health; Centers for Disease Control and, Prevention; HIV Medicine Association of the Infectious Diseases Society of, America (May 2014). "Prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Updated Guidelines from the Centers for Disease Control and Prevention, National Institutes of Health, and HIV Medicine Association of the Infectious Diseases Society of America". Clinical Infectious Diseases. 58 (9): 1308–11. doi:10.1093/cid/ciu094. PMC 3982842. PMID 24585567.
  3. ^ "Prescribing medicines in pregnancy database". Australian Government. 3 March 2014. from the original on 8 April 2014. Retrieved 22 April 2014.
  4. ^ a b c Huovinen, P (1 June 2001). "Resistance to trimethoprim-sulfamethoxazole". Clinical Infectious Diseases. 32 (11): 1608–14. doi:10.1086/320532. PMID 11340533.
  5. ^ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
  6. ^ Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 113. ISBN 9781284057560.
  7. ^ a b c Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
  8. ^ Pradhan E, Bhandari S, Gilbert RE, Stanford M (May 2016). "Antibiotics versus no treatment for toxoplasma retinochoroiditis" (PDF). Cochrane Database Syst Rev. 2016 (5): CD002218. doi:10.1002/14651858.CD002218.pub2. PMC 7100541. PMID 27198629.
  9. ^ "Three-day courses of antibiotics for uncomplicated urinary tract infection | Guidance and guidelines | NICE". from the original on 2015-12-08. Retrieved 2015-12-30.
  10. ^ "DailyMed - TRIMETHOPRIM- trimethoprim tablet". dailymed.nlm.nih.gov. from the original on 2015-09-30. Retrieved 2015-11-04.
  11. ^ "DailyMed - PRIMSOL- trimethoprim hydrochloride solution". dailymed.nlm.nih.gov. from the original on 2015-11-17. Retrieved 2015-11-04.
  12. ^ "PROLOPRIM® (trimethoprim)100-mg and 200-mg Scored Tablets". dailymed.nlm.nih.gov. from the original on 2015-11-17. Retrieved 2015-11-04.
  13. ^ Ellenhorn, M.J.; S. Schonwald; G. Ordog; J. Wasserberger. American Hospital Formulary Service- Drug Information 2002. Baltimore, MD: Williams and Wilkins. p. 236.
  14. ^ MICROMEDEX Thomson Health Care. USPDIpublisher = Thomson Health. Drug Information for the Health Care Professional. 22nd ed. Volume 1. CareGreenwood Village, CO. 2002 p. 2849.{{cite book}}: CS1 maint: location (link)
  15. ^ Choi, Michael J.; Fernandez, Pedro C.; Patnaik, Asit; Coupaye-Gerard, Brigitte; D'Andrea, Denise; Szerlip, Harold; Kleyman, Thomas R. (1993-03-11). "Trimethoprim-Induced Hyperkalemia in a Patient with AIDS". New England Journal of Medicine. 328 (10): 703–706. doi:10.1056/NEJM199303113281006. ISSN 0028-4793. PMID 8433730.
  16. ^ Naderer, O.; Nafziger, A. N.; Bertino, J. S. (1997-11-01). "Effects of moderate-dose versus high-dose trimethoprim on serum creatinine and creatinine clearance and adverse reactions". Antimicrobial Agents and Chemotherapy. 41 (11): 2466–2470. doi:10.1128/AAC.41.11.2466. ISSN 0066-4804. PMC 164146. PMID 9371351.
  17. ^ Kimmitt PT, Harwood CR, Barer MR (2000). "Toxin Gene Expression by Shiga Toxin-producing Escherichia coli: The Role of Antibiotics and the Bacterial SOS Response". Emerg Infect Dis. 6 (5): 458–465. doi:10.3201/eid0605.000503. PMC 2627954. PMID 10998375.
  18. ^ "DailyMed - PRIMSOL- trimethoprim hydrochloride solution". dailymed.nlm.nih.gov. from the original on 2015-11-17. Retrieved 2015-11-04.
  19. ^ Sivojelezova, Anna; Einarson, Adrienne; Shuhaiber, Samar; Koren, Gideon (2003-09-01). "Trimethoprim-sulfonamide combination therapy in early pregnancy". Canadian Family Physician. 49: 1085–1086. ISSN 0008-350X. PMC 2214286. PMID 14526858.
  20. ^ Edwards DL, Fink PC, van Dyke PO (1986). "Disulfiram-like reaction associated with intravenous trimethoprim-sulfamethoxazole and metronidazole". Clinical Pharmacy. 5 (12): 999–1000. PMID 3492326. from the original on 2009-01-24.
  21. ^ Heelon MW, White M (1998). "Disulfiram cotrimoxazole reaction". J Pharmacotherapy. 18 (4): 869–870. doi:10.1002/j.1875-9114.1998.tb03913.x. PMID 9692665. S2CID 23968977. from the original on 2009-01-24.
  22. ^ Andersen JT, Petersen M, Jimenez-Solem E, Broedbaek K, Andersen EW, Andersen NL, Afzal S, Torp-Pedersen C, Keiding N, Poulsen HE (2013). "Trimethoprim use in early pregnancy and the risk of miscarriage: a register-based nationwide cohort study". Epidemiology and Infection. 141 (8): 1749–1755. doi:10.1017/S0950268812002178. PMC 9151599. PMID 23010291. S2CID 19917493.
  23. ^ Heaslet, H.; Harris, M.; Fahnoe, K.; Sarver, R.; Putz, H.; Chang, J.; Subramanyam, C.; Barreiro, G.; Miller, J. R. (2009). "Structural comparison of chromosomal and exogenous dihydrofolate reductase from Staphylococcus aureusin complex with the potent inhibitor trimethoprim". Proteins: Structure, Function, and Bioinformatics. 76 (3): 706–717. doi:10.1002/prot.22383. PMID 19280600. S2CID 1373618.
  24. ^ a b c d Brogden, RN; Carmine, AA; Heel, RC; Speight, TM; Avery, GS (June 1982). "Trimethoprim: a review of its antibacterial activity, pharmacokinetics and therapeutic use in urinary tract infections". Drugs. 23 (6): 405–30. doi:10.2165/00003495-198223060-00001. PMID 7049657. S2CID 21806926.
  25. ^ Burchall, James J. (1973). "Mechanism of Action of Trimethoprim-Sulfamethoxazole: II". The Journal of Infectious Diseases. 128: 437–441. doi:10.1093/infdis/128.Supplement_3.S437. JSTOR 30105875. PMID 4585969.
  26. ^ Brumfitt, W; Hamilton-Miller, JM (December 1993). "Reassessment of the rationale for the combinations of sulphonamides with diaminopyrimidines". Journal of Chemotherapy. 5 (6): 465–9. doi:10.1080/1120009X.1993.11741097. PMID 8195839.

External links

  • "Trimethoprim". Drug Information Portal. U.S. National Library of Medicine.

January 30, 2023
trimethoprim, confused, with, thymidine, monophosphate, antibiotic, used, mainly, treatment, bladder, infections, other, uses, include, middle, infections, travelers, diarrhea, with, sulfamethoxazole, dapsone, used, pneumocystis, pneumonia, people, with, aids,. Not to be confused with Thymidine monophosphate Trimethoprim TMP is an antibiotic used mainly in the treatment of bladder infections 1 Other uses include for middle ear infections and travelers diarrhea 1 With sulfamethoxazole or dapsone it may be used for Pneumocystis pneumonia in people with HIV AIDS 1 2 It is taken by mouth 1 TrimethoprimClinical dataPronunciation t r aɪ ˈ m ɛ 8 e p r ɪ m Trade namesProloprim Monotrim Triprim othersAHFS Drugs comMonographMedlinePlusa684025License dataUS FDA TrimethoprimPregnancycategoryAU B3Routes ofadministrationOralDrug classDiaminopyrimidinesATC codeJ01EA01 WHO QJ51EA01 WHO Legal statusLegal statusAU S4 Prescription only CA only UK POM Prescription only US onlyPharmacokinetic dataBioavailability90 100 Protein binding44 MetabolismhepaticElimination half life8 12 hoursExcretionUrine 50 60 faeces 4 IdentifiersIUPAC name 5 3 4 5 Trimethoxybenzyl pyrimidine 2 4 diamineCAS Number738 70 5 YPubChem CID5578DrugBankDB00440 YChemSpider5376 YUNIIAN164J8Y0XKEGGD00145 YChEBICHEBI 45924 YChEMBLChEMBL22 YPDB ligandTOP PDBe RCSB PDB CompTox Dashboard EPA DTXSID3023712ECHA InfoCard100 010 915Chemical and physical dataFormulaC 14H 18N 4O 3Molar mass290 323 g mol 13D model JSmol Interactive imageSMILES Nc1nc N ncc1Cc cc2OC cc OC c2OCInChI 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 YKey IEDVJHCEMCRBQM UHFFFAOYSA N Y verify Common side effects include nausea changes in taste and rash 1 Rarely it may result in blood problems such as not enough platelets or white blood cells 1 Trimethoprim may cause sun sensitivity 1 There is evidence of potential harm during pregnancy in some animals but not humans 3 It works by blocking folate metabolism via dihydrofolate reductase in some bacteria which results in their death 1 Trimethoprim was first used in 1962 4 It is on the World Health Organization s List of Essential Medicines 5 It is available as a generic medication 6 Contents 1 Medical uses 1 1 Spectrum of susceptibility 2 Side effects 2 1 Common 2 2 Rare 2 3 Contraindications 2 4 Pregnancy 3 Mechanism of action 4 History 5 See also 6 References 7 External linksMedical uses EditIt is primarily used in the treatment of urinary tract infections although it may be used against any susceptible aerobic bacterial species 7 It may also be used to treat and prevent Pneumocystis jirovecii pneumonia 7 It is generally not recommended for the treatment of anaerobic infections such as Clostridium difficile colitis the leading cause of antibiotic induced diarrhea 7 Trimethoprim has been used in trials to treat retinitis 8 Resistance to trimethoprim is increasing but it is still a first line antibiotic in many countries 9 Spectrum of susceptibility Edit Cultures and susceptibility tests should be done to make sure bacteria are treated by trimethoprim 10 11 Escherichia coli Proteus mirabilis Klebsiella pneumoniae Enterobacter species Coagulase negative Staphylococcus species including S saprophyticus Streptococcus pneumoniae Haemophilus influenzaeSide effects EditCommon Edit Nauseas Change in taste Vomiting Diarrhea Rashes Sun sensitivity Itchiness 12 13 Rare Edit Can cause thrombocytopenia low levels of platelets by lowering folic acid levels this may also cause megaloblastic anemia 14 Trimethoprim antagonizes the epithelial sodium channel in the distal tubule thus acting like amiloride This can cause increased potassium levels in the body hyperkalemia 15 Can compete with creatinine for secretion into the renal tubule This can cause an artificial rise in the serum creatinine 16 Use in EHEC infections may lead to an increase in expression of Shiga toxin 17 Contraindications Edit Known hypersensitivity to trimethoprim History of megaloblastic anemia due to folate deficiency 18 Pregnancy Edit Based on the studies that show that trimethoprim crosses the placenta and can affect folate metabolism there has been growing evidence of the risk of structural birth defects associated with trimethoprim especially during the first trimester of pregnancy 19 It may be involved in a reaction similar to disulfiram when alcohol is consumed after it is used in particular when used in combination with sulfamethoxazole 20 21 The trophoblasts in the early fetus are sensitive to changes in the folate cycle A recent study has found a doubling in the risk of miscarriage in women exposed to trimethoprim in the early pregnancy 22 Mechanism of action Edit Staphylococcus aureus DHFR in complex with NADPH and trimethoprim PDB entry 2W9G 23 Trimethoprim binds to dihydrofolate reductase and inhibits the reduction of dihydrofolic acid DHF to tetrahydrofolic acid THF 24 THF is an essential precursor in the thymidine synthesis pathway and interference with this pathway inhibits bacterial DNA synthesis 24 Trimethoprim s inhibitory activity for bacterial dihydrofolate reductase is sixty thousand times greater than for human dihydrofolate reductase 25 Sulfamethoxazole inhibits dihydropteroate synthase an enzyme involved further upstream in the same pathway 24 Trimethoprim and sulfamethoxazole are commonly used in combination due to possible synergistic effects and reduced development of resistance 24 This benefit has been questioned 26 Tetrahydrofolate synthesis pathwayHistory EditTrimethoprim was first used in 1962 4 In 1972 it was used as a prophylactic treatment for urinary tract infections in Finland 4 Its name is derived from trimethyloxy pyrimidine See also EditTetroxoprim IclaprimReferences Edit a b c d e f g h Trimethoprim The American Society of Health System Pharmacists Archived from the original on 2015 09 24 Retrieved Aug 1 2015 Masur H Brooks JT Benson CA Holmes KK Pau AK Kaplan JE National Institutes of Health Centers for Disease Control and Prevention HIV Medicine Association of the Infectious Diseases Society of America May 2014 Prevention and treatment of opportunistic infections in HIV infected adults and adolescents Updated Guidelines from the Centers for Disease Control and Prevention National Institutes of Health and HIV Medicine Association of the Infectious Diseases Society of America Clinical Infectious Diseases 58 9 1308 11 doi 10 1093 cid ciu094 PMC 3982842 PMID 24585567 Prescribing medicines in pregnancy database Australian Government 3 March 2014 Archived from the original on 8 April 2014 Retrieved 22 April 2014 a b c Huovinen P 1 June 2001 Resistance to trimethoprim sulfamethoxazole Clinical Infectious Diseases 32 11 1608 14 doi 10 1086 320532 PMID 11340533 World Health Organization 2021 World Health Organization model list of essential medicines 22nd list 2021 Geneva World Health Organization hdl 10665 345533 WHO MHP HPS EML 2021 02 Hamilton Richart 2015 Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab Coat Edition Jones amp Bartlett Learning p 113 ISBN 9781284057560 a b c Rossi S ed 2013 Australian Medicines Handbook 2013 ed Adelaide The Australian Medicines Handbook Unit Trust ISBN 978 0 9805790 9 3 Pradhan E Bhandari S Gilbert RE Stanford M May 2016 Antibiotics versus no treatment for toxoplasma retinochoroiditis PDF Cochrane Database Syst Rev 2016 5 CD002218 doi 10 1002 14651858 CD002218 pub2 PMC 7100541 PMID 27198629 Three day courses of antibiotics for uncomplicated urinary tract infection Guidance and guidelines NICE Archived from the original on 2015 12 08 Retrieved 2015 12 30 DailyMed TRIMETHOPRIM trimethoprim tablet dailymed nlm nih gov Archived from the original on 2015 09 30 Retrieved 2015 11 04 DailyMed PRIMSOL trimethoprim hydrochloride solution dailymed nlm nih gov Archived from the original on 2015 11 17 Retrieved 2015 11 04 PROLOPRIM trimethoprim 100 mg and 200 mg Scored Tablets dailymed nlm nih gov Archived from the original on 2015 11 17 Retrieved 2015 11 04 Ellenhorn M J S Schonwald G Ordog J Wasserberger American Hospital Formulary Service Drug Information 2002 Baltimore MD Williams and Wilkins p 236 MICROMEDEX Thomson Health Care USPDIpublisher Thomson Health Drug Information for the Health Care Professional 22nd ed Volume 1 CareGreenwood Village CO 2002 p 2849 a href Template Cite book html title Template Cite book cite book a CS1 maint location link Choi Michael J Fernandez Pedro C Patnaik Asit Coupaye Gerard Brigitte D Andrea Denise Szerlip Harold Kleyman Thomas R 1993 03 11 Trimethoprim Induced Hyperkalemia in a Patient with AIDS New England Journal of Medicine 328 10 703 706 doi 10 1056 NEJM199303113281006 ISSN 0028 4793 PMID 8433730 Naderer O Nafziger A N Bertino J S 1997 11 01 Effects of moderate dose versus high dose trimethoprim on serum creatinine and creatinine clearance and adverse reactions Antimicrobial Agents and Chemotherapy 41 11 2466 2470 doi 10 1128 AAC 41 11 2466 ISSN 0066 4804 PMC 164146 PMID 9371351 Kimmitt PT Harwood CR Barer MR 2000 Toxin Gene Expression by Shiga Toxin producing Escherichia coli The Role of Antibiotics and the Bacterial SOS Response Emerg Infect Dis 6 5 458 465 doi 10 3201 eid0605 000503 PMC 2627954 PMID 10998375 DailyMed PRIMSOL trimethoprim hydrochloride solution dailymed nlm nih gov Archived from the original on 2015 11 17 Retrieved 2015 11 04 Sivojelezova Anna Einarson Adrienne Shuhaiber Samar Koren Gideon 2003 09 01 Trimethoprim sulfonamide combination therapy in early pregnancy Canadian Family Physician 49 1085 1086 ISSN 0008 350X PMC 2214286 PMID 14526858 Edwards DL Fink PC van Dyke PO 1986 Disulfiram like reaction associated with intravenous trimethoprim sulfamethoxazole and metronidazole Clinical Pharmacy 5 12 999 1000 PMID 3492326 Archived from the original on 2009 01 24 Heelon MW White M 1998 Disulfiram cotrimoxazole reaction J Pharmacotherapy 18 4 869 870 doi 10 1002 j 1875 9114 1998 tb03913 x PMID 9692665 S2CID 23968977 Archived from the original on 2009 01 24 Andersen JT Petersen M Jimenez Solem E Broedbaek K Andersen EW Andersen NL Afzal S Torp Pedersen C Keiding N Poulsen HE 2013 Trimethoprim use in early pregnancy and the risk of miscarriage a register based nationwide cohort study Epidemiology and Infection 141 8 1749 1755 doi 10 1017 S0950268812002178 PMC 9151599 PMID 23010291 S2CID 19917493 Heaslet H Harris M Fahnoe K Sarver R Putz H Chang J Subramanyam C Barreiro G Miller J R 2009 Structural comparison of chromosomal and exogenous dihydrofolate reductase from Staphylococcus aureusin complex with the potent inhibitor trimethoprim Proteins Structure Function and Bioinformatics 76 3 706 717 doi 10 1002 prot 22383 PMID 19280600 S2CID 1373618 a b c d Brogden RN Carmine AA Heel RC Speight TM Avery GS June 1982 Trimethoprim a review of its antibacterial activity pharmacokinetics and therapeutic use in urinary tract infections Drugs 23 6 405 30 doi 10 2165 00003495 198223060 00001 PMID 7049657 S2CID 21806926 Burchall James J 1973 Mechanism of Action of Trimethoprim Sulfamethoxazole II The Journal of Infectious Diseases 128 437 441 doi 10 1093 infdis 128 Supplement 3 S437 JSTOR 30105875 PMID 4585969 Brumfitt W Hamilton Miller JM December 1993 Reassessment of the rationale for the combinations of sulphonamides with diaminopyrimidines Journal of Chemotherapy 5 6 465 9 doi 10 1080 1120009X 1993 11741097 PMID 8195839 External links Edit Trimethoprim Drug Information Portal U S National Library of Medicine Portal Medicine Retrieved from https en wikipedia org w index php title Trimethoprim amp oldid 1135317508, wikipedia, wiki, book, books, library,

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