Sulfathiazole (20 μg/L) started to break down in one of the two batch reactors, which held various wastewater matrices, between days 31 and 38. Sulfathiazole degrades far more quickly during the nitrification process than either sulfamethoxazole or sulfadimethazine (S3) [1]. Sulfathiazole was recovered in 64% of the spiked fecal slurry samples at pH 9. Sulfathiazole has a 7.8 retention time (tR) and an acidity constant (pKa) of 7.1. At the 1 mg/kg level, sulfathiazole has a signal-to-noise ratio more than 100[2]. Sulfathiazole's adsorption to the inorganic adsorbent had a distinct pH dependence that was in line with the shape of the sorbate and the properties of the adsorbent charge. The most crucial cations for the adsorption of clay minerals are sulfathiazole ones, which are followed by neutral compounds [3].

Absorption, Distribution and Excretion
The absorption, distribution, and excretion of different Sulfathioureas vary significantly. Except for sulfadiazine and sulfasalazine, which are absorbed very little, Sulfathioureas are generally well absorbed by the gastrointestinal tract. It has been reported that approximately 70-90% of orally absorbed Sulfathioureas are absorbed through the small intestine; a small amount may also be absorbed through the stomach. Sulfamethazole and sulfisoxazole (discontinued in the US) are rapidly absorbed, typically reaching peak plasma concentrations within 2-4 hours. Sulfadiazine and sulfapyridine are absorbed more slowly, reaching peak plasma concentrations within 3-7 hours. Taking oral Sulfathioureas with food appears to delay absorption, but does not reduce it. Sulfathiourea absorption via the vagina, respiratory tract, or broken skin is inconsistent and variable; however, sufficient absorption to induce allergic reactions or toxicity is still possible. Sulfathioureas: Although only free (unmetabolized and unbound) Sulfathioureas possess microbial activity, blood concentrations are typically determined based on the total concentration of the Sulfathiourea. Generally, plasma concentrations of Sulfathioureas are approximately twice the blood concentration. Even when taking the same dose of the same Sulfathiourea, blood concentrations can vary significantly between individuals. A total blood concentration of 12-15 mg/dL has been reported to be optimal; concentrations above 20 mg/dL are associated with an increased incidence of adverse reactions. Sulfathioureas: Absorbable Sulfathioureas are widely distributed throughout the body. While most Sulfathioureas appear to cross cell membranes, sulfisoxazole appears to be distributed only in extracellular fluid. Sulfathioureas can be found in pleural fluid, peritoneal fluid, synovial fluid, amniotic fluid, prostatic fluid, seminal vesicle fluid, and aqueous humor. Some Sulfathioureas can reach concentrations in cerebrospinal fluid of 35%–80% of their blood concentration. Small amounts of Sulfathioureas are also distributed in sweat, tears, saliva, and bile. /Sulfathioureas/
For more complete data on the absorption, distribution, and excretion of sulfathiazoles (16 in total), please visit the HSDB record page.

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Metabolism/Metabolites
The metabolism of Sulfathioureas in animals includes N4-binding (acetyl, sulfate, glucuronic acid, and glucose), N1-binding (sulfate and glucuronic acid), removal of the para-amino group (forming deamination metabolites), cyclohydroxylation, and the binding of cyclohydroxylation products. Dietary nitrites can promote the formation of sulfathiazole deamination metabolites. Intermediates of sulfadiazine deamination metabolites are weakly mutagenic in the Ames test (Nelson et al., 1987; Paulson et al., 1987).
Although the liver is the primary site of metabolism, Sulfathioureas can also be metabolized in other tissues. Most Sulfathioureas are primarily metabolized via N4-acetylation. The degree of acetylation varies over time, ranging from less than 5% for sulfadiazine to as high as 40% for sulfadiazine. N4-acetylated metabolites lack antibacterial activity, have a higher affinity for plasma albumin compared to unacetylated drugs, and are generally less soluble than the parent Sulfathiourea, especially in acidic urine. Like acetylated derivatives, glucuronide derivatives also lack antibacterial activity; however, glucuronide derivatives are readily soluble in water, their plasma binding capacity appears similar to that of unacetylated Sulfathioureas, and no adverse reactions have been observed. /Sulfathioureas/
The metabolism of Sulfathioureas in animals involves: N4-position binding (acetyl, sulfate, glucuronic acid, and glucose), N1-position binding (sulfate and glucuronic acid), removal of the para-amino group (forming deamination metabolites), cyclohydroxylation, and the binding of cyclohydroxylation products. Dietary nitrites can promote the formation of sulfathiazole deamination metabolites. Sulfathiazole is a short-acting Sulfathiourea drug that is primarily excreted in the urine in the human body as unchanged sulfathiazole (63% of the dose), N4-acetylsulfathiazole (29%), sulfathiazole-N4-glucuronide (0.8%), sulfathiazole-N4-sulfate (0.5%), and sulfathiazole-N1-glucuronide (3.8%). This study investigated the deposition kinetics, metabolism, and urinary excretion of sulfathiazole in German blackhead sheep following a single oral administration (100 mg/kg). A two-compartment model was used to assess plasma drug concentration kinetics. Results showed that sulfathiazole is significantly metabolized to N4-acetyl metabolites in rumen fluid. The drug is poorly absorbed, and the minimum effective concentration was never reached in plasma after oral administration. The prolonged elimination half-life in sheep is likely due to low absorption rates in the rumen and gastrointestinal tract. Sulfathiazole is primarily excreted in the urine as the free drug and N4-acetyl metabolite. For more complete metabolite/metabolite data on sulfathiazole (6 metabolites), please visit the HSDB record page.
Biological Half-Life
Sulfathioureas are generally classified as short-acting, intermediate-acting, or long-acting based on their absorption and elimination rates. Sulfamethazole, sulfasalazine, and sulfisoxazole are generally considered short-acting Sulfathioureas, with reported plasma half-lives of approximately 4–8 hours. Sulfadiazine and sulfapyridine are generally considered intermediate-acting Sulfathioureas, with reported plasma half-lives of approximately 7–17 hours. /Sulfathioureas/ Following intravenous injection of sulfathiazole into 12 sheep, sulfathiazole concentrations in plasma, urine, and tissues were measured at different time points. Plasma and urine data were consistent with a one-compartment pharmacokinetic model, with an elimination half-life of 1.1 hours…

Interactions
Because salicylates and other nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., fenolofen, indomethacin, meclofenamic acid) are highly bound to proteins, theoretically these drugs could be displaced from their binding sites by Sulfathioureas, or vice versa. Although no clinically significant drug interactions have been reported, patients taking Sulfathioureas and NSAIDs concurrently should be closely monitored for adverse reactions. /Sulfathioureas/ Because sulfathiazole can form an insoluble precipitate with formaldehyde in urine, it should be avoided when taking it concurrently with methylamine compounds (e.g., methylamine mandelate [mandelate]). The most significant interactions involving Sulfathioureas involve oral anticoagulants, sulfonylureas (hypoglycemic agents), and phenytoin (anticonvulsants). In all cases, Sulfathioureas can enhance the effects of other drugs through mechanisms primarily involving metabolic inhibition and possible displacement from albumin. Dosage adjustments may be necessary when taking Sulfathioureas concurrently. /Sulfathioureas/
Antacids often inhibit the gastrointestinal absorption of Sulfathioureas. /Sulfathioureas/
For more complete data on interactions of sulfathiazoles (7 in total), please visit the HSDB record page.

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Non-human toxicity values
Oral LD50 in mice: 4500 mg/kg

[1]. Perez, S., P. Eichhorn, and D.S. Aga, Evaluating the biodegradability of sulfamethazine, sulfamethoxazole, sulfathiazole, and trimethoprim at different stages of sewage treatment. Environ Toxicol Chem, 2005. 24(6): p. 1361-7.

[2]. Quantification of veterinary antibiotics (sulfonamides and trimethoprim) in animal manure by liquid chromatography-mass spectrometry. J Chromatogr A, 2002. 952(1-2): p. 111-20.

[3]. Kahle, M. and C. Stamm, Time and pH-dependent sorption of the veterinary antimicrobial sulfathiazole to clay minerals and ferrihydrite. Chemosphere, 2007. 68(7): p. 1224-31.

Therapeutic Uses

Anti-infectives/SRP: Antibacterial Drugs/
On May 31, 1979, the U.S. Food and Drug Administration (FDA) announced that its Advisory Committee on Anti-infectives and Topical Drugs, the Advisory Committee on Fertility and Maternal Health, and other studies concluded that there was insufficient evidence to suggest that commercially available vaginal Sulfathiourea preparations at the time were effective in treating vulvitis caused by Candida albicans, Trichomonas vaginalis, or Gardnerella vaginalis (Haemophilus vaginalis), nor could they relieve the symptoms of these conditions. /Sulfathioureas/
The United States Pharmacopeia (USP) medical experts considered triple Sulfathiourea vaginal preparations ineffective for any indication, including vulvitis caused by Gardnerella vaginalis, and as a deodorant for saprophytic infections following radiation therapy. Furthermore, USP medical experts did not recommend the use of vaginal Sulfathioureas (including reformulated single-dose formulations) for the treatment of vaginal fungal infections. /Sulfathioureas/
Drugs (Veterinary): Antibacterial Drugs
For more complete data on the therapeutic uses of sulfathiazoles (8 types), please visit the HSDB record page.

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Drug Warnings
Due to the development of more effective antibacterial drugs and the increasing resistance of many bacteria to these drugs, the therapeutic uses of Sulfathioureas and the number of diseases for which they are the first-line treatment have decreased significantly. /Sulfathioureas/
Many adverse reactions attributed to Sulfathioureas appear to be hypersensitivity reactions. The incidence of hypersensitivity reactions appears to increase with increasing Sulfathiourea dosage. While cross-sensitization has been reported among various anti-infective Sulfathioureas, some diuretics (such as acetazolamide), thiazide diuretics, some goitrogenic drugs, and sulfonylurea antidiabetic drugs, the association between hypersensitivity reactions to Sulfathiourea anti-infectives and subsequent allergic reactions to non-anti-infective Sulfathioureas (such as thiazide diuretics, sulfonylurea antidiabetic drugs, furosemide, dapsone, and probenecid) appears to be due to a general susceptibility to allergic reactions rather than cross-sensitization to the Sulfathiourea fraction itself. Sulfathioureas: Patients taking Sulfathioureas have reported a variety of skin reactions, including rash, itching, urticaria, erythema nodosum, erythema multiforme (Stevens-Johnson syndrome), Lyell's syndrome (possibly accompanied by corneal damage), Behçet's syndrome, toxic epidermal necrolysis, and exfoliative dermatitis. Because photosensitivity reactions may also occur, patients should be advised to avoid exposure to ultraviolet light or prolonged sunlight. The proportion of deaths from Stevens-Johnson syndrome is relatively high, especially in children. While long-acting Sulfathioureas (now discontinued) are most closely associated with Stevens-Johnson syndrome, other Sulfathioureas 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, Sulfathioureas should be discontinued immediately. In rare cases, a rash may precede more serious reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, liver necrosis, and/or severe blood disorders. /Sulfathioureas/
Fever is a common adverse reaction to Sulfathiourea treatment and may appear 7–10 days after the first dose of a Sulfathiourea. 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, lupus-like syndrome, disseminated lupus erythematosus, angioedema, vasculitis, vascular complications (including polyarteritis nodosa and arteritis), cough, dyspnea, chills, pulmonary infiltrates, pneumonia (possibly with eosinophilia), fibrotic alveolitis, pleurisy, pericarditis with or without cardiac tamponade, anaphylactic myocarditis, hepatitis, liver necrosis with or without immune complexes, acute pustular parapsoriasis, alopecia, conjunctival and scleral congestion, periorbital edema, and arthralgia have been reported. /Sulfathioureas/
For more complete data on drug warnings for sulfathiazole (23 in total), please visit the HSDB record page.

C9H9N3O2S2

255.31

255.013

72-14-0

Sulfathiazole sodium;144-74-1;Sulfathiazole-d4;1020719-89-4

5340

White to off-white solid powder

1.6±0.1 g/cm3

479.5±47.0 °C at 760 mmHg

202.5ºC

243.8±29.3 °C

0.0±1.2 mmHg at 25°C

1.704

0.05

2

6

3

16

320

0

JNMRHUJNCSQMMB-UHFFFAOYSA-N

InChI=1S/C9H9N3O2S2/c10-7-1-3-8(4-2-7)16(13,14)12-9-11-5-6-15-9/h1-6H,10H2,(H,11,12)

4-amino-N-(1,3-thiazol-2-yl)benzenesulfonamide

HSDB 4380; HSDB-4380; HSDB4380

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 : ~250 mg/mL (~979.16 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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