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Also known as: Sulfamethoxazole & trimethoprim, Sulfamethoxazole + trimethoprim, Co-trimoxazole, Trimosulfa, Cotrimoxazole, Septra

Molecular Formula

C₂₄H₂₉N₇O₆S

Molecular Weight

543.6 g/mol

InChI Key

WZRJTRPJURQBRM-UHFFFAOYSA-N

A drug combination with broad-spectrum antibacterial activity against both gram-positive and gram-negative organisms. It is effective in the treatment of many infections, including PNEUMOCYSTIS PNEUMONIA in AIDS.

1 2D Structure

Septrin

2 Identification

2.1 Computed Descriptors

2.1.1 IUPAC Name

4-amino-N-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide;5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidine-2,4-diamine

2.1.2 InChI

InChI=1S/C14H18N4O3.C10H11N3O3S/c1-19-10-5-8(6-11(20-2)12(10)21-3)4-9-7-17-14(16)18-13(9)15;1-7-6-10(12-16-7)13-17(14,15)9-4-2-8(11)3-5-9/h5-7H,4H2,1-3H3,(H4,15,16,17,18);2-6H,11H2,1H3,(H,12,13)

2.1.3 InChI Key

WZRJTRPJURQBRM-UHFFFAOYSA-N

2.1.4 Canonical SMILES

CC1=CC(=NO1)NS(=O)(=O)C2=CC=C(C=C2)N.COC1=CC(=CC(=C1OC)OC)CC2=CN=C(N=C2N)N

2.2 Synonyms

2.2.1 MeSH Synonyms

1. Abactrim

2. Bactifor

3. Bactrim

4. Biseptol

5. Biseptol 480

6. Biseptol-480

7. Biseptol480

8. Centran

9. Centrin

10. Co Trimoxazole

11. Co-trimoxazole

12. Cotrimoxazole

13. Drylin

14. Eslectin

15. Eusaprim

16. Insozalin

17. Kepinol

18. Kepinol Forte

19. Lescot

20. Metomide

21. Oriprim

22. Septra

23. Septrin

24. Sulfamethoxazole Trimethoprim Combination

25. Sulfamethoxazole-trimethoprim Combination

26. Sulprim

27. Sumetrolim

28. Tmp Smx

29. Tmp-smx

30. Trimedin

31. Trimethoprim Sulfamethoxazole

32. Trimethoprim Sulfamethoxazole Combination

33. Trimethoprim, Sulfamethoxazole Drug Combination

34. Trimethoprim-sulfamethoxazole

35. Trimethoprim-sulfamethoxazole Combination

36. Trimethoprimsulfa

37. Trimezole

38. Trimosulfa

2.2.2 Depositor-Supplied Synonyms

1. Sulfamethoxazole & Trimethoprim

2. Sulfamethoxazole + Trimethoprim

3. Co-trimoxazole

4. Trimosulfa

5. Cotrimoxazole

6. Septra

7. 8064-90-2

8. Trimethoprimsulfa

9. Trimforte

10. Sulfamethoxazole-trimethoprim

11. Trimethoprim-sulfamethoxazole

12. Tmp-smx

13. Gantrim

14. Trimethoprim-sulfamethoxazole Combination

15. Trimethoprim/sulfamethoxazole

16. Tmp/smx

17. Trimethoprim And Sulphamethoxazole

18. Sulfamethoxazole Trimethoprim

19. Sulfamethoxazole / Trimethoprim

20. Trimethoprim And Sulfamethoxazole

21. Sulfamethoxazole Mixture With Trimethoprim

22. Nsc618652

23. Abactrim

24. Biseptol

25. Eusaprim

26. Kepinol

27. Oriprim

28. Sulprim

29. Sumetrolim

30. Drylin

31. Kepinol Forte

32. Septra Grape

33. Septra Ds

34. Bactrim Ds

35. Bactrim Pediatric

36. Uroplus Ds

37. Uroplus Ss

38. Sulfatrim Pediatric

39. Sulmeprim Pediatric

40. Aposulfatrim

41. Bactoreduct

42. Cotrimhexal

43. Cotrimoxazol

44. Cotrimstada

45. Duratrimet

46. Jenamoxazol

47. Sulfotrimin

48. Supracombin

49. Trimetoger

50. Trimexazol

51. Agoprim

52. Alfatrim

53. Bacteral

54. Bactilen

55. Bactiver

56. Bactrizol

57. Bactromin

58. Bactropin

59. Berlocid

60. Bibacrim

61. Chemitrim

62. Chemotrim

63. Cotribene

64. Cotriver

65. Dibaprim

66. Eltrianyl

67. Escoprim

68. Esteprim

69. Fectrim

70. Gantaprim

71. Gantaprin

72. Groprim

73. Helveprim

74. Kemoprim

75. Laratrim

76. Linaris

77. Maxtrim

78. Microtrim

79. Mikrosid

80. Momentol

81. Oecotrim

82. Oxaprim

83. Pantoprim

84. Primazole

85. Septrim

86. Septrin

87. Servitrim

88. Sigaprim

89. Sigaprin

90. Sulfotrim

91. Tacumil

92. Teleprim

93. Teleprin

94. Thiocuran

95. Tribakin

96. Trigonyl

97. Trimesulf

98. Uroplus

99. Abacin

100. Bacton

101. Baktar

102. Ciplin

103. Comox

104. Imexim

105. Nopil

106. Omsat

107. Suprim

108. Trifen

109. Bacterial Forte

110. Microtrim Forte

111. Duon

112. Trimetho Comp

113. Cotrimox-wolff

114. Bactrim Forte

115. Co-trimaxazol

116. Cotrim Holsen

117. Cotrimoxazol Al

118. Cotrim-puren

119. Strepto-plus

120. Cotrim-hefa

121. Trimexole-f

122. Baktrisid-ds

123. Co-trim-tablinen

124. Cotrim-radiopharm

125. Sulfa-tyl

126. Sulfameth/tmp

127. Sulfameth/trimeth

128. Cotrim Eu Rho

129. Cotrim_basf

130. Cotrimoxazol-cophar

131. 4-amino-n-(5-methylisoxazol-3-yl)benzenesulfonamide Compound With 5-(3,4,5-trimethoxybenzyl)pyrimidine-2,4-diamine (1:1)

132. Benzenesulfonamide, 4-amino-n-(5-methyl-3-isoxazolyl)-, Mixt. With 5-[(3,4,5-trimethoxyphenyl)methyl]-2,4-pyrimidinediamine

133. Cotrim D.s.

134. Cotrim.l.u.t.

135. Smx-tmp

136. Smx/tmp

137. Sulfamethoxazole-trimeth

138. Sulfamethoxazole / Tmp

139. Smx / Tmp

140. Tmp / Smx

141. Co-trimazole

142. A 033

143. Hsdb 6780

144. Tms 480

145. Benzenesulfonamide, 4-amino-n-(5-methyl-3-isoxazolyl)-, Mixt. With 5-((3,4,5-trimethoxyphenyl)methyl)-2,4-pyrimidinediamine

146. Bactrim (tn)

147. Septra (tn)

148. Nsc 618652

149. Sulfamethoxazole And Trimethoprim Double Strength

150. Sulfamethoxazole And Trimethoprim Single Strength

151. Co-trimoxazole (ban)

152. Epitope Id:141805

153. Tmp & Smx

154. Trimethoprim, Sulfamethoxazole Drug Combination

155. Chembl58061

156. Schembl870329

157. Trimethoprim & Sulfamethoxazole

158. Chebi:3770

159. Dtxsid0032233

160. Nsc-618652

161. Sulfamethoxazole - Trimethoprim Mixture

162. Benzenesulfonamide, 4-a)mino-n-(5-methyl-3-isoxazolyl)-, Mixt. With 5-((3,4,5-trimethoxyphenyl)methyl-2,4-pyrimidinediamine

163. D00285

164. Q898623

165. Benzenesulfonamide, Mixt. With 5-[(3,4,5-trimethoxyphenyl)methyl]-2,4- Pyrimidinediamine

166. 4-amino-n-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide;5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidine-2,4-diamine

167. 4-amino-n-(5-methylisoxazol-3-yl)benzenesulfonamide; 5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidine-2,4-diamine

168. 50808-41-8

169. Benzenesulfonamide, 4-amino-n-(5-methyl-3-isoxazolyl)- & 5-((3,4,5-trimethoxyphenyl)methyl)-2,4-pyrimidinediamine

170. Pyrimidine, 2,4-diamino-5-(3,4,5-trimethoxybenzyl)- And N'-(5-methyl-3-isoxazolyl)sulfanilamide

171. Sxt

2.3 Create Date

2005-03-26

3 Chemical and Physical Properties

Molecular Formula	C₂₄H₂₉N₇O₆S
Molecular Weight	543.6 g/mol
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	13
Rotatable Bond Count	8
Exact Mass	543.19000284 g/mol
Monoisotopic Mass	543.19000284 g/mol
Topological Polar Surface Area	212 Å²
Heavy Atom Count	38
Formal Charge	0
Complexity	653
Isotope Atom Count	0
Defined Atom Stereocenter Count	0
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
Covalently Bonded Unit Count	2

4 Drug and Medication Information

4.1 Drug Information

1 of 4
Drug Name	Septra
Active Ingredient	trimethoprim; Sulfamethoxazole
Dosage Form	Tablet
Route	Oral
Strength	400mg; 80mg
Market Status	Prescription
Company	Monarch Pharms

2 of 4
Drug Name	Sulfamethoxazole and trimethoprim single strength
Active Ingredient	trimethoprim; Sulfamethoxazole
Dosage Form	Tablet
Route	Oral
Strength	400mg; 80mg
Market Status	Prescription
Company	Teva Pharms

3 of 4
Drug Name	Sulfamethoxazole and trimethoprim double strength
Drug Label	BACTRIM (
Active Ingredient	trimethoprim; Sulfamethoxazole
Dosage Form	Tablet
Route	Oral
Strength	160mg; 800mg
Market Status	Prescription
Company	Teva

4 of 4
Drug Name	Sulfamethoxazole and trimethoprim
Active Ingredient	trimethoprim; Sulfamethoxazole
Dosage Form	Tablet; Suspension; Injectable
Route	Injection; Oral
Strength	80mg/ml; 200mg/5ml; 160mg; 40mg/5ml; 400mg; 800mg; 16mg/ml; 80mg
Market Status	Prescription
Company	Aurobindo Pharma; Teva Pharms Usa; Vista Pharms; Glenmark Generics; Amneal Pharms Ny; Hi Tech Pharma; Mutual Pharm; Vintage

4.2 Therapeutic Uses

Anti-Infective Agents; Anti-Infective Agents, Urinary; Antimalarials

National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)

Co-trimoxazole has been used in the treatment of gonorrhea caused by penicillinase-producing Neisseria gonorrhoeae. Although other anti-infective agents are generally recommended by the US Centers for Disease Control and many clinicians for the treatment of urogenital or anorectal infections caused by penicillinase-producing Neisseria gonorrhoeae, co-trimoxazole may be effective for the treatment of pharyngeal infections caused by penicillinase-producing Neisseria gonorrhoeae Although clinical experience is limited, oral co-trimoxazole may also be effective as an alternative to currently recommended regimens for the treatment of acute sexually transmitted epididymitis caused by penicillinase-producing Neisseria gonorrhoeae.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992)., p. 463

Trimethoprim/sulfamethoxazole is an alternative to tetracycline in cholera. This combination is recommended in isosporiasis (Isospora belli).

American Medical Association. AMA Drug Evaluations Annual 1991. Chicago, IL: American Medical Association, 1991., p. 1345

Trimethoprim/sulfamethoxazole may be useful in serious infections, including meningitis, osteomyelitis, bacteremia, and endocarditis, caused by susceptible gram-negative bacteria when other antibacterial agents are ineffective or not tolerated. Of particular note, gram-negative bacillary meningitis caused by organisms only moderately susceptible to third generation cephalosporins (eg, Enterobacter cloacae, Serratia marcescens) or resistant to these antibiotics (Acinetobacter, Pseudomonas cepacia) may be candidates for trimethoprim/sulfamethoxazole therapy if the organisms are susceptible. This combination may be an effective alternative to ampicillin (or penicillin G) with or without an aminoglycoside for the treatment of meningitis and bacteremia caused by Listeria monocytogenes. Trimethoprim/sulfamethoxazole may be useful for the treatment of infective endocarditis caused by Coxiella burnetii. In a double-blind, randomized, prospective study, intravenous trimethoprim/sulfamethoxazole (640 mg/3200 mg daily) was shown to be as effective as vancomycin in the treatment of serious methicillin-resistant Staphylococcus aureus infections, including bacteremias, endocarditis, septic arthritis, and osteomyelitis. The details of this study have not been published, however, and some consultants expressed concern about the use of trimethoprim/sulfamethoxazole in deep-seated staphylococcal infections (eg, endocarditis) because this combination may only be bacteriostatic against this organism. Currently, each of these indications is considered investigational.

American Medical Association. AMA Drug Evaluations Annual 1991. Chicago, IL: American Medical Association, 1991., p. 1346

For more Therapeutic Uses (Complete) data for TRIMETHOPRIM/SULFAMETHOXAZOLE (25 total), please visit the HSDB record page.

4.3 Drug Warning

Trimethoprim-sulfamethoxazole should not be used to treat streptococcal pharyngitis, since it does not eradicate the microorganism.

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 1056

Since serious reactions such as the Stevens-Johnson syndrome have occurred in some individuals, therapy should be discontinued at the first appearance of skin rash or other adverse effects.

Hussar, D.A. (ed.). Modell's Drugs in Current Use and New Drugs. 38th ed. New York, NY: Springer Publishing Co., 1992., p. 165

May increase the action of warfarin and phenytoin.

Hussar, D.A. (ed.). Modell's Drugs in Current Use and New Drugs. 38th ed. New York, NY: Springer Publishing Co., 1992., p. 165

Should not be used in pregnancy at term or during the nursing period.

Hussar, D.A. (ed.). Modell's Drugs in Current Use and New Drugs. 38th ed. New York, NY: Springer Publishing Co., 1992., p. 165

For more Drug Warnings (Complete) data for TRIMETHOPRIM/SULFAMETHOXAZOLE (13 total), please visit the HSDB record page.

5 Pharmacology and Biochemistry

5.1 MeSH Pharmacological Classification

Anti-Infective Agents, Urinary

Substances capable of killing agents causing urinary tract infections or of preventing them from spreading. (See all compounds classified as Anti-Infective Agents, Urinary.)

Anti-Bacterial Agents

Substances that inhibit the growth or reproduction of BACTERIA. (See all compounds classified as Anti-Bacterial Agents.)

Antimalarials

Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585) (See all compounds classified as Antimalarials.)

5.2 FDA Pharmacological Classification

5.2.1 Pharmacological Classes

Cytochrome P450 2C9 Inhibitors [MoA]; Dihydrofolate Reductase Inhibitor Antibacterial [EPC]; Dihydrofolate Reductase Inhibitors [MoA]; Organic Cation Transporter 2 Inhibitors [MoA]; Sulfonamide Antimicrobial [EPC]; Sulfonamides [CS]; Cytochrome P450 2C8 Inhibitors [MoA]

5.3 ATC Code

J - Antiinfectives for systemic use

J01 - Antibacterials for systemic use

J01E - Sulfonamides and trimethoprim

J01EE - Combinations of sulfonamides and trimethoprim, incl. derivatives

J01EE01 - Sulfamethoxazole and trimethoprim

5.4 Absorption, Distribution and Excretion

Co-trimoxazole is widely distributed into body tissues and fluids, including sputum, aqueous humor, middle ear fluid, prostatic fluid, vaginal fluid, bile, and cerebrospinal fluid; trimethoprim also distributes into bronchial secretions. Trimethoprim has a larger volume of distribution than does sulfamethoxazole. In adults, apparent volume of distribution of 100-120 and 12-18 l have been reported for trimethoprim and sulfamethoxazole, respectively. In patients with uninflamed meninges, trimethoprim and sulfamethoxazole concentrations in cerebrospinal fluid are about 50 and 40%, respectively, of concurrent serum concentrations of the drugs. Trimethoprim and sulfamethoxazole concentrations in middle ear fluid are approximately 75 and 20%, respectively, and in prostatic fluid are approximately 200 and 35%, respectively, of concurrent serum concentrations of the drugs.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992)., p. 461

After a single oral dose of the combined preparation, trimethoprim is absorbed more rapidly than sulfamethoxazole. The concurrent administration of the drugs appears to slow the absorption of sulfamethoxazole. Peak blood concentrations of trimethoprim ususally occur by 2 hours in most patients, while peak concentrations of sulfamethoxazole occur by 4 hours after a single oral dose.

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 1055

Trimethoprim is rapidly distributed and concentrated in tissues, and about 40% is bound to plasma protein in the presence of sulfamethoxazole. The volume of distribution of trimethoprim is almost nine times that of sulfamethoxazole. The drug readily enters cerebrospinal fluid and sputum. High concentrations of each component of the mixture are also found in bile.

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 1055

The pharmacokinetics of trimethoprim-sulfamethoxazole were studied in 12 healthy adult subjects receiving trimethoprim at 20 mg/kg of body weight per day and sulfamethoxazole at 100 mg/kg/day, which is the conventional dose for treating Pneumocystis carinii pneumonia. Daily doses were evenly divided and orally administered every 6 h for 3 days. Trimethoprim, sulfamethoxazole, and N4-acetylsulfamethoxazole concn in serum and urine were measured by HPLC. Five subjects withdrew from the study because of intolerable GI and CNS toxicities. In the seven subjects that completed the study, the mean maximum serum drug concn after the last dose were 13.6 + or - 2.0, 372 + or - 64, and 50.1 + or - 10.9 ug/ml for trimethoprim, sulfamethoxazole, and N4-acetylsulfamethoxazole, respectively. The mean half-lives were 13.6 + or - 3.5, 14.0 + or - 2.3, and 18.6 + or - 4.3 hr, respectively. Changes in absolute neutrophil count were significantly correlated with the minimum concn of trimethoprim and sulfamethoxazole in serum and trimethoprim area under the concn-time curve (for all three parameters, r2 = 0.6 and p < 0.05). These findings add to the evidence that serum drug concn in adults following the conventional dose of trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia are excessive and contribute to certain adverse reactions.

Stevens RC et al; Antimicrob Agents Chemother 35 (9): 1991 1884-90 (1990)

This article reviews the pharmacokinetics, clinical use, and adverse effects of trimethoprim/sulfamethoxazole in renally impaired patients. Renal dysfunction changes the pharmacokinetics of both component drugs. Trimethoprim and sulfamethoxazole disposition are not significantly altered until creatinine clearance is less than 30 ml/min, when sulfamethoxazole metabolites and trimethoprim accumulate and may lead to toxicity. Renal dysfunction, however, does not preclude the use of trimethoprim/sulfamethoxazole to treat susceptible infections, even when creatinine clearance is less than 15 ml/min. Adverse effects may occur more frequently in renally impaired patients but are not clearly related to increased serum concentrations of either drug. Guidelines for appropriate dosing and monitoring of trimethoprim/sulfamethoxazole therapy in these patients are presented.

PMID:2678767 Paap CM, Nahata MC; DICP 23 (9): 646-54 (1989)

5.5 Metabolism/Metabolites

Co-trimoxazole is metabolized in the liver. Trimethoprim is metabolized to oxide and hydroxylated metabolites and sulfamethoxazole is principally N-acetylated and also conjugated with glucuronic acid. Both drugs are rapidly excreted in urine via glomerular filtration and tubular secretion. In adults with normal renal function, approximately 50-60% of a trimethoprim and 45-70% of a sulfamethoxazole oral dose are excreted in urine within 24 hours. Approximately 80% of the amount of trimethoprim and 20% of the amount of sulfamethoxazole recovered in urine are unchanged drug. In adults with normal renal function, urinary concentrations of active trimethoprim are approximately equal to those of active sulfamethoxazole. Urinary concentrations of both active drugs are decreased in patients with impaired renal function.

McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992)., p. 461

5.6 Biological Half-Life

The half-lives of trimethoprim and sulfamethoxazole are approximately 11 and 10 hours, respectively.

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 1055

5.7 Mechanism of Action

Trimethoprim/sulfamethoxazole ... inhibits sequential steps in the synthesis of tetrahydrofolic acid, an essential metabolic cofactor in the bacterial synthesis of purines, thymidine, glycine, and methionine. Sulfonamides, including sulfamethoxazole, are structural analogues of para-aminobenzoic acid and block the synthesis of dihydropteroic acid, the immediate precursor of dihydrofolic acid, from para-aminobenzoic acid and peridine. Trimethoprim subsequently acts to inhibit the reduction of dihydrofolic acid to the metabolically active tetrahydrofolic acid by the enzyme, dihydrofolate reductase. The most important consequence of this sequential enzymatic inhibition appears to be the interruption of thymidine synthesis.

American Medical Association. AMA Drug Evaluations Annual 1991. Chicago, IL: American Medical Association, 1991., p. 1343

The synergistic interaction between sulfonamide and trimethoprim is thus predictable from their respective mechanisms. There is an optimal ratio of the concentrations of the two agents for synergism, and this is equal to the ratio of the minimal inhibitory concentrations of the drugs acting independently. While this ratio varies for different bacteria, the most effective ratio for the greatest number of microorganisms is 20 parts of sulfamethoxazole to one part of trimethoprim. The combination is formulated to achieve a sulfamethoxazole concentration in vivo 20 times greater than that of trimethoprim. ... The pharmacokinetic properties of the sulfonamide chosen to be in combination with trimethoprim are important, since relative constancy of the concentrations of the two compounds in the body is desired.

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 1054

Trimethoprim/sulfamethoxazole is active in vitro against a variety of gram-negative and gram-postive bacteria. Among aerobic gram-negative enteric bacteria, Escherichia coli, Proteus mirabilis, Salmonella (including Salmonella typhi), Shigella, and Citrobacter are very susceptible. Indole-positive Proteus, Serratia marcescens, Klebsiella pneumoniae, Enterobacter, Providencia stuartii are moderately susceptible.

American Medical Association. AMA Drug Evaluations Annual 1991. Chicago, IL: American Medical Association, 1991., p. 1344

An immunoassay was developed for the detection of sulfamethoxazole reactive IgE antibodies in the sera of patients who experienced life threatening anaphylactic reactions following the ingestion of co-trimoxazole (trimethoprim and sulfamethoxazole). Patients who had significant levels of sulfamethoxazole reactive IgE antibodies in their sera did not have IgE antibodies that reacted with trimethoprim-Sepharose. Inhibition experiments with a number of sulfonamides to determine the fine structural specificities of the sulfamethoxazole reactive IgE antibodies in three patients revealed that sulfamethoxazole and, depending on the serum, sulfamerazine and sulfamethizole, were the most potent inhibitors of IgE binding, whereas the parent sulfonamide, sulfanilamide, was a very poor inhibitor. From a detailed examination of structure-activity relationships, we concluded that the 5-methyl-3-isoxazolyl group on the sulfamethoxazole molecule was the allergenic determinant for all three patients with the 5-methyl group being particularly important for IgE antibody recognition. The assays for the detection of IgE antibodies to sulfamethoxazole and trimethoprim should prove useful for the diagnosis of immediate hypersensitivity to co-trimoxazole and perhaps for monitoring drug therapy in AIDS patients where a high incidence of adverse reactions to co-trimoxazole has been reported.

PMID:3237218 Harle DG et al; Mol Immunol 25 (12): 1347-54 (1988)

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