Absorption, Distribution and Excretion
Absorption is rapid. Sulfamethoxazole is readily absorbed from the gastrointestinal tract. In a small number of patients, after a single oral dose of 2 grams of sulfamethoxazole, plasma concentrations reach approximately 30 μg/mL within 1 hour. Peak plasma concentrations reach approximately 60 μg/mL within 2 hours, then gradually decrease, falling to 6.6 μg/mL within 8 hours and 5 μg/mL within 12 hours. Approximately 2-11% of sulfamethoxazole in the blood exists in its N4-acetylated form. Sulfamethoxazole is distributed to most body tissues but does not appear to diffuse into the cerebrospinal fluid of patients with normal meninges. Sulfamethoxazole binds to plasma proteins at a rate of approximately 90%. Due to its rapid excretion in the urine, the manufacturer notes that very little sulfamethoxazole accumulates in tissues outside the urinary system. Sulfamethoxazole…is a rapidly excreted sulfonamide; therefore, blood concentrations are low after taking a standard dose. Approximately 80% of the administered dose is recovered within 8 hours; approximately 98% of the drug is cleared within 15 to 24 hours. The renal clearance rate of sulfamethoxazole is only 10% to 20% lower than that of creatinine. For more complete data on absorption, distribution, and excretion of sulfamethoxazole (21 items in total), please visit the HSDB record page. Metabolism/Metabolites Hepatic metabolism. Approximately 95% of sulfamethoxazole doses are not metabolized; less than 5% of sulfamethoxazole is acetylated. Therefore, almost all given doses of sulfamethoxazole are present in the body in their active form. Metabolites N4-acetylated sulfonamides have renal clearance rates 6–20 times higher than their parent compounds. Sulfamethoxazole is minimally acetylated. While the liver is the primary site of metabolism, sulfonamides may also be metabolized in other tissues. Most sulfonamides are primarily metabolized via N4-acetylation. The degree of acetylation varies over time, ranging from less than 5% for sulfamethoxazole to as high as 40% for sulfadiazine. N4-acetyl metabolites lack antibacterial activity, have a higher affinity for plasma albumin compared to unacetylated drugs, and are generally less soluble than the parent sulfonamide, especially in acidic urine. Like acetylated derivatives, glucuronide derivatives lack antibacterial activity; however, glucuronide derivatives are readily soluble in water, their plasma binding capacity appears similar to that of unacetylated sulfonamides, and no adverse reactions have been observed. /Sulfonamides/

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Biological Half-Life
3-8 hours
Sulfonamides are generally classified as short-acting, intermediate-acting, or long-acting based on their absorption and elimination rates. Sulfamethoxazole, sulfasalazine, and sulfisoxazole are generally considered short-acting sulfonamides, with reported plasma half-lives of approximately 4-8 hours. Sulfadiazine and sulfapyridine are generally considered intermediate-acting sulfonamides, with reported plasma half-lives of approximately 7-17 hours. /Sulfonamides/

Protein Binding
98-99% Interactions: Some sulfonamides may displace coumarin or indanedione derivative anticoagulants, phenytoin anticonvulsants, or oral hypoglycemic agents from their protein binding sites and/or inhibit their metabolism, leading to enhanced or prolonged effects and/or toxicity; dose adjustments may be necessary during and after sulfonamide treatment. Sulfonamides: Concomitant use of sulfonamides with myelosuppressants may increase leukopenia and/or thrombocytopenia; if concomitant use is necessary, close monitoring for myelotoxicity is required. Sulfonamides: Long-term concomitant use of sulfonamides with estrogen-containing oral contraceptives may increase the incidence of breakthrough bleeding and pregnancy. Sulfonamides: Concomitant use of sulfonamides with cyclosporine may increase cyclosporine metabolism, leading to decreased plasma concentrations and potentially causing transplant rejection and additive nephrotoxicity; plasma cyclosporine concentrations and renal function should be monitored. Sulfonamides
For more complete data on interactions of sulfamethoxazoles (12 in total), please visit the HSDB record page.
Non-human toxicity values

Oral LD50 in rats: 3500 mg/kg

Sulfamethizole is a white powder. (NTP, 1992)
Sulfamethizole is a sulfonamide compound composed of a 1,3,4-thiadiazole ring with a methyl substituent at the C-5 position and a 4-aminobenzenesulfonamide group at the C-2 position. It possesses multiple functions including antibacterial activity, EC 2.5.1.15 (dihydropterolate synthase) inhibition, anti-infective activity, and drug allergen activity. It is a sulfonamide compound belonging to the thiadiazole class of antibiotics.
Sulfamethizole is a sulfathiazole antibacterial agent.
It has been reported that sulfathiazole is present in the Chinese honeybee (Apis cerana), and relevant data are available.
Sulfamethizole is a broad-spectrum sulfonamide compound and a synthetic analog of para-aminobenzoic acid (PABA), possessing antibacterial activity. Sulfathiazole competes with para-aminobenzoic acid (PABA) for the bacterial enzyme dihydropteroate synthase, thereby preventing PABA from being incorporated into dihydrofolate (a direct precursor of folic acid). This leads to inhibition of bacterial folic acid synthesis as well as de novo synthesis of purines and pyrimidines, ultimately resulting in cell growth arrest and cell death.
Sulfathiazole antibacterial agents.
See also: Methylamine mandelate; Sulfathiazole (component).
Indications
For the treatment of urinary tract infections.
Mechanism of Action
Sulfathiazole is a competitive inhibitor of the bacterial enzyme dihydropteroate synthase. The normal substrate para-aminobenzoic acid (PABA) cannot bind. This inhibitory response is essential for folic acid synthesis in these microorganisms.
Sulfonamides generally have antibacterial activity. Sulfonamides interfere with the utilization of para-aminobenzoic acid (PABA) in susceptible bacteria in the biosynthesis of tetrahydrofolate (the reduced form of folic acid) cofactors. Sulfonamides are structural analogues of PABA, and they appear to interfere with PABA utilization by competitively inhibiting dihydropteranoic acid synthase. Dihydropteranoic acid synthase catalyzes the reaction of PABA and pteridine to produce dihydropteranoic acid (a precursor to tetrahydrofolate); however, other mechanisms affecting biosynthetic pathways may also be involved. Compounds such as pyrimethamine and trimethoprim block later steps in folic acid synthesis and synergistically interact with sulfonamides. Only microorganisms capable of synthesizing folic acid themselves are inhibited by sulfonamides; animal cells and bacteria capable of utilizing folic acid precursors or pre-formed folic acid are unaffected. The antibacterial activity of sulfonamides has been reported to decrease in the presence of blood or purulent exudates. /Sulfonamides/
Sulfonamides are structural analogues of para-aminobenzoic acid (PABA), and they competitively inhibit the enzymatic step of dihydropteranoic acid synthase, in which PABA is incorporated into the synthesis of dihydrofolate (folic acid). Due to reduced synthesis of dihydrofolate, the level of tetrahydrofolate (folinic acid), derived from dihydrofolate, also decreases. Tetrahydrofolate is a crucial component of coenzymes required for intracellular single-carbon metabolism. Sulfonamides, acting as antimetabolites of PABA, ultimately block the activity of multiple enzymes in a complex manner. These enzymes include those required for purine base biosynthesis; the transfer of deoxyuridine to thymidine; and the biosynthesis of methionine, glycine, and formylmethionine transfer RNA. This leads to inhibition of protein synthesis, impaired metabolic processes, and suppression of the growth and reproduction of microorganisms unable to utilize pre-formed folic acid. While its effect is bacteriostatic, it also exhibits significant bactericidal activity at high concentrations that may be present in urine.

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Therapeutic Use
Anti-infectives/SRP: Antibacterial Drugs/
Sulfamethoxazole is indicated for the treatment of urinary tract infections (primarily pyelonephritis, pyelonephritis, and cystitis) caused by susceptible strains of the following bacteria, without obstructive urinary tract disease or foreign bodies: Escherichia coli, Klebsiella pneumoniae-Enterobacter spp., Staphylococcus aureus, Proteus mirabilis, and Proteus vulgaris. /Included on US Product Label/
Sulfonamides are indicated for the treatment of chancroid caused by Haemophilus ducreyi. However, other drugs such as erythromycin and ceftriaxone are considered as first-line treatments. /Sulfonamides; Included on US Product Label/
Sulfonamides are indicated for the treatment of cervical and urinary tract infections caused by Chlamydia trachomatis. However, other drugs such as doxycycline and azithromycin are considered as first-line treatments. /Sulfonamides; Included on US Product Label/
For more complete data on the therapeutic uses of sulfamethoxazole (17 in total), please visit the HSDB record page.

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Drug Warning
Due to the development of more effective antibacterial drugs and the increasing resistance of various bacteria to these drugs, the therapeutic use and number of indications for sulfonamides as first-line drugs have decreased significantly. /Sulfonamides/
Many adverse reactions attributed to sulfonamides appear to be hypersensitivity reactions. The incidence of hypersensitivity reactions appears to increase with increasing sulfonamide dosage. Although cross-sensitization has been reported among various anti-infective sulfonamides, some diuretics (such as acetazolamide) and thiazide diuretics, some goitrogenic drugs, and sulfonylurea antidiabetic drugs, the association between hypersensitivity reactions to sulfonamide anti-infectives and subsequent allergic reactions to non-anti-infective sulfonamides (such as thiazide diuretics, sulfonylurea antidiabetic drugs, furosemide, dapsone, probenecid) appears to be due to a general susceptibility to allergic reactions rather than cross-sensitization to the sulfonamide fraction itself. Sulfonamides: Patients taking sulfonamides have reported a variety of skin reactions, including rash, itching, urticaria, erythema nodosum, erythema multiforme (Stevens-Johnson syndrome), Lyle's syndrome (possibly accompanied by corneal damage), Behcet's syndrome, toxic epidermal necrolysis, and exfoliative dermatitis. Because photosensitivity reactions can also occur, patients should be advised to avoid exposure to ultraviolet light or prolonged sunlight. The proportion of deaths due to Stevens-Johnson syndrome is relatively high, especially in children. While long-acting sulfonamides (currently discontinued) are most closely associated with Stevens-Johnson syndrome, other sulfonamides have also been reported to cause this reaction. Physicians should be alert to signs that may precede skin lesions in Stevens-Johnson syndrome, including high fever, severe headache, stomatitis, conjunctivitis, rhinitis, urethritis, and balanitis. If a rash develops during treatment, sulfonamides should be discontinued immediately. In rare cases, the rash may precede more serious reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, liver necrosis, and/or severe blood disorders. /Sulfonamides/
Fever is a common adverse reaction to sulfonamide treatment and may appear 7–10 days after the first dose of a sulfonamide. Serum sickness syndrome or serum sickness-like reactions (e.g., fever, chills, shivering, flushing, arthralgia, urticarial rash, conjunctivitis, bronchospasm, leukopenia) have been reported; in rare cases, anaphylactic reactions and anaphylactic shock may occur. In addition, it has been reported in cases of lupus-like syndrome, disseminated lupus erythematosus, angioedema, vasculitis, vascular lesions (including polyarteritis nodosa and arteritis), cough, dyspnea, chills, pulmonary infiltrates, pneumonia (possibly with eosinophilia), fibrotic alveolitis, pleurisy, pericarditis with or without cardiac tamponade, allergic myocarditis, hepatitis, liver necrosis with or without immune complexes, acute pustular parapsoriasis, alopecia, conjunctival and scleral congestion, periorbital edema, and arthralgia. /Sulfonamides/
For more complete data on drug warnings for Sulfamethizole (27 in total), please visit the HSDB record page.

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Pharmacodynamics
Sulfamethizole is a sulfonamide antibiotic. Sulfonamides are synthetic antibacterial antibiotics with broad-spectrum antibacterial activity against most Gram-positive bacteria and many Gram-negative bacteria. However, many strains of the same species may develop resistance. Sulfonamides inhibit bacterial growth by competitively inhibiting para-aminobenzoic acid in the folic acid metabolic cycle. Bacteria have similar sensitivity to various sulfonamides; resistance to one sulfonamide implies resistance to all sulfonamides. Most sulfonamides are well absorbed orally. However, parenteral administration is challenging due to the strong alkalinity and tissue irritation of soluble sulfonamide salts. Sulfonamides are widely distributed in all tissues. High concentrations are found in pleural effusions, ascites, synovial fluid, and intraocular fluid. Although these drugs are no longer used to treat meningitis, high concentrations of sulfonamides remain in cerebrospinal fluid during meningeal infections. Pus can inhibit their antibacterial activity.

C9H12N4O2S2

272.341

270.024

144-82-1

Sulfamethizole-d4;Sulfamethizole-d4-1;2470130-12-0

5328

Crystals from water
Colorless crystal

1.6±0.1 g/cm3

504.9±52.0 °C at 760 mmHg

210 °C

259.1±30.7 °C

0.0±1.3 mmHg at 25°C

1.687

0.51

2

7

3

17

349

0

S(C1C([H])=C([H])C(=C([H])C=1[H])N([H])[H])(N([H])C1=NN=C(C([H])([H])[H])S1)(=O)=O

VACCAVUAMIDAGB-UHFFFAOYSA-N

InChI=1S/C9H10N4O2S2/c1-6-11-12-9(16-6)13-17(14,15)8-4-2-7(10)3-5-8/h2-5H,10H2,1H3,(H,12,13)

4-amino-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzenesulfonamide

RP-2145; RP2145; RP 2145

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 100 mg/mL (~369.92 mM)
H2O : ~0.67 mg/mL (~2.48 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.25 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (9.25 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)