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
Individual sulfonamides differ markedly in their absorption, distribution, and elimination. With the exception of sulfapyrimidine and sulfasalazine, which are only slightly absorbed, sulfonamides are generally well absorbed from the GI tract. Approximately 70-90% of an oral dose of the absorbable sulfonamides is reportedly absorbed from the small intestine; small amounts may also be absorbed from the stomach. Sulfamethizole and sulfisoxazole (no longer commercially available in the US) are absorbed rapidly; peak blood concentrations are usually obtained within 2-4 hours. Sulfadiazine and sulfapyridine are absorbed at a slower rate with peak blood concentrations occurring within 3-7 hours. Administration of oral sulfonamides with food appears to delay, but not reduce, absorption of the drugs. /Sulfonamides/
Absorption of sulfonamides from the vagina, respiratory tract, or abraded skin is variable and unreliable; however, enough drug may be absorbed to induce sensitization or toxicity. /Sulfonamides/
Although only free (unmetabolized and unbound) sulfonamides are microbiologically active, blood concentrations are often determined on the basis of total sulfonamide concentration. Generally, sulfonamide plasma concentrations are approximately twice the blood concentrations. Wide variations in blood concentrations have been reported in different individuals receiving identical doses of the same sulfonamide. Blood total sulfonamide concentrations of 12-15 mg/dL have been reported to be optimal; blood concentrations greater than 20 mg/dL have been associated with an increased incidence of adverse reactions. /Sulfonamides/
Absorbable sulfonamides are widely distributed in the body. Although most sulfonamides appear to cross cell membranes, sulfisoxazole appears to be distributed only in extracellular fluid. Sulfonamides may appear in pleural, peritoneal, synovial, amniotic, prostatic, and seminal vesicular fluid, and aqueous humor. Concentrations of some sulfonamides in the CSF may reach 35-80% of blood concentrations. Small amounts of sulfonamides are also distributed into sweat, tears, saliva, and bile. /Sulfonamides/
For more Absorption, Distribution and Excretion (Complete) data for SULFATHIAZOLE (16 total), please visit the HSDB record page.

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Metabolism / Metabolites
Metabolism of sulfonamide drugs in animals includes conjugation at the N4-position (acetyl, sulfate, glucuronic acid, and glucose), conjugation at the N1-position (sulfate and glucuronic acid), removal of the p-amino group (formation of the desamino metabolite), ring hydroxylation, and conjugation of the ring hydroxylation products. Dietary nitrite enhances the production of the desamino metabolite of sulfathiazole. The intermediate leading to the desamino metabolite of sulfamethazine is weakly mutagenic in the Ames test (Nelson et al., 1987; Paulson et al., 1987).
Although the liver is the major site of metabolism, sulfonamides may also be metabolized in other body tissues. Most sulfonamides are metabolized mainly by N4-acetylation. The degree of acetylation, which is a function of time, varies from less than 5% for sulfamethizole to up to 40% for sulfadiazine. The N4-acetyl metabolites, which do not possess antibacterial activity, have greater affinity for plasma albumin than does the nonacetylated drug and are usually less soluble than the parent sulfonamide, particularly in acidic urine. Like acetyl derivatives, glucuronide derivatives do not possess antibacterial activity; however, glucuronide derivatives are water soluble, appear to resemble the nonacetylated sulfonamide in plasma binding capacity, and have not been associated with adverse effects. /Sulfonamides/
Metabolism of sulfonamide drugs in animals includes conjugation at the N4-position (acetyl, sulfate, glucuronic acid, and glucose), conjugation at the N1-position (sulfate and glucuronic acid), removal of the p-amino group (formation of the desamino metabolite), ring hydroxylation, and conjugation of the ring hydroxylation products. Dietary nitrite enhances the production of the desamino metabolite of sulfathiazole.
Sulfathiazole...is one of the short-acting sulfonamides & in man is excreted in urine as unchanged sulfathiazole (63% of dose), N4-acetylsulfathiazole (29%), sulfathiazole-N4-glucuronide (0.8%), sulfathiazole-N4-sulfate (0.5%) & sulfathiazole-N1-glucuronide (3.8%).
Deposition kinetics, metabolism and urinary excretion of sulfathiazole were investigated in German black head sheep following single oral administration (100 mg/kg). Kinetic evaluation of plasma levels was performed using a two-compartment best fit model. Sulfathiazole is significantly metabolized to N4-acetyl metabolite in the rumen fluid. The drug is very poorly absorbed since the minimum effective concentration in plasma was not attained at any time following oral administration. The prolonged elimination half-life in sheep may be due to a low rate of drug absorption from the rumen and gastro-intestinal tract. Sulfathiazole was mainly excreted in the urine as free drug and N4-acetyl metabolite.
For more Metabolism/Metabolites (Complete) data for SULFATHIAZOLE (6 total), please visit the HSDB record page.

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Biological Half-Life
Sulfonamides are generally classified as short-acting, intermediate-acting, or long-acting depending on the rate at which they are absorbed and eliminated. Sulfamethizole, sulfasalazine, and sulfisoxazole are generally considered to be short-acting sulfonamides and reportedly have plasma half-lives of about 4-8 hours. Sulfadiazine and sulfapyridine are generally considered to be intermediate-acting sulfonamides and reportedly have plasma half-lives of about 7-17 hours. /Sulfonamides/
The plasma, urine, and tissue sulfathiazole concentrations were determined at various times following intravenous administration to 12 sheep. The plasma and urine data were consistent with a one-compartment pharmacokinetic model, with an elimination half-life of 1.1 hr...

Interactions
Since salicylates and other nonsteroidal anti-inflammatory agents (e.g., fenoprofen, indomethacin, meclofenamate) are highly protein bound, these drugs theoretically could be displaced from binding sites by sulfonamides, or could displace sulfonamides from binding sites. Although no clinically important drug interactions have been reported, patients receiving sulfonamides concomitantly with nonsteroidal anti-inflammatory agents should be observed for adverse effects. /Sulfonamides/
Because...sulfathiazole may form insoluble precipitates with formaldehyde in the urine, their concomitant administration with methenamine compounds (eg, methenamine mandelate [mandelamine]) should be avoided.
The most important interactions of the sulfonamides involve those with the oral anticoagulants, the sulfonylurea hypoglycemic agents, and the hydantoin anticonvulsants. In each case, sulfonamides can potentiate the effects of the other drug by mechanisms that appear to involve primarily inhibition of metabolism and, possibly, displacement from albumin. Dosage adjustment may be necessary when a sulfonamide is given concurrently. /Sulfonamides/
Antacids tend to inhibit the GI absorption of sulfonamides. /Sulfonamides/
For more Interactions (Complete) data for SULFATHIAZOLE (7 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Mouse oral 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-Infective Agents /SRP: Antibacterial/
The US FDA announced on May 31, 1979, that its Anti-infective and Topical Drugs Advisory Committee and Fertility and Maternal health Advisory Committee, as well as other studies, had concluded there was no adequate evidence that the then-available vaginal sulfonamides formulations were effective either for the treatment of vulvovaginitis caused by Candida albicans, trichomonas vaginalis, or Gardnerella vaginalis (Hemophilus vaginalis) or for relief of the symptoms of these conditions. /Sulfonamides/
In the opinion of USP medical experts, triple sulfa vaginal preparations are not effective for any indication, including vulvovaginitis caused by Gardnerella vaginalis and use as a deodorant in saprophytic infections following radiation therapy. Also, USP medical experts do not recommend the use of vaginal sulfonamides, including the reformulated single-entry preparations, for the treatment of fungal infections of the vagina. /Sulfonamides/
MEDICATION (VET): Antibacterial
For more Therapeutic Uses (Complete) data for SULFATHIAZOLE (8 total), please visit the HSDB record page.

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Drug Warnings
The number of conditions for which the sulfonamides are therapeutically useful and constitute drugs of first choice has been reduced sharply by the development of more effective antimicrobial agents and by the gradual increase in the resistance of a number of bacterial species to this class of drugs. /Sulfonamides/
Many of the adverse effects that have been attributed to the sulfonamides appear to be hypersensitivity reactions. The incidence of hypersensitivity reactions appears to increase with increased sulfonamide dosage. Although cross-sensitization has been reported to occur between the various anti-infective sulfonamides, some diuretics such as acetazolamide and the thiazides, some goitrogens, and sulfonylurea antidiabetic agents, the association between hypersensitivity to sulfonamide anti-infectives and subsequent sensitivity reactions to non-anti-infective sulfonamides (e.g., thiazides, sulfonylurea antidiabetic agents, furosemide, dapsone, probenecid) appears to result from a predisposition to allergic reactions in general rather than to cross-sensitivity to the sulfa moiety per se. /Sulfonamides/
Various dermatologic reactions, including rash, pruritus, urticaria, erythema nodosum, erythema multiforme (Stevens-Johnson syndrome), Lyell's syndrome (may be associated with corneal damage), Behcet's syndrome, toxic epidermal necrolysis, and exfoliative dermatitis, have been reported in patients receiving sulfonamides. Because photosensitivity may also occur, patients should be cautioned against exposure to UV light or prolonged exposure to sunlight. A relatively high proportion of fatalities has occurred as a result of the Stevens-Johnson syndrome, especially in children. Although long-acting sulfonamides (which are no longer commercially available) have been associated most often with the Stevens-Johnson syndrome, other sulfonamides also have been reported to cause this reaction. The physician should be alert to the signs, including high fever, severe headache, stomatitis, conjunctivitis, rhinitis, urethritis, and balanitis, which may precede the onset of the cutaneous lesions of the Stevens-Johnson syndrome. If a rash develops during therapy, the sulfonamide should be discontinued at once. In rare instances, a skin rash may precede a more serious reaction such as Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic necrosis, and/or serious blood disorders. /Sulfonamides/
Fever, which may develop 7-10 days after the initial sulfonamide dose, is a common adverse effect of sulfonamide therapy. Serum sickness syndrome or serum sickness-like reactions (e.g., fever, chills, rigors, flushing, joint pain, urticarial eruptions, conjunctivitis, bronchospasm, leukopenia), have been reported; rarely, anaphylactoid reactions and anaphylaxis may occur. Lupus erythematosus-like syndrome, disseminated lupus erythematosus, angioedema, vasculitis, vascular lesions including periarteritis nodosa and arteritis, cough, shortness of breath, chills, pulmonary infiltrates, pneumonitis (which may be associated with eosinophilia), fibrosing alveolitis, pleuritis, pericarditis with or without tamponade, allergic myocarditis, hepatitis, hepatic necrosis with or without immune complexes, parapsoriasis varioliformis acuta, alopecia, conjunctival and scleral injection, periorbital edema, and arthralgia have also been reported. /Sulfonamides/
For more Drug Warnings (Complete) data for SULFATHIAZOLE (23 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.)