Sulfathiazole

255.32

255.32

200-771-5

Y7FKS2XWQH

757331|683531|31812

DTXSID8026068

C66571

Brown plates, rods or powder from 45% alcohol|Yellowish-white prismatic rods and six sided plates and prisms

D06BA02|D - Dermatologicals|J - Antiinfectives for systemic use

2935009090

122

0.1

Sulfathiazole is a white crystalline powder. Is dimorphous: form I is consists of prismatic rods and form II of six-sided plates and prisms. Insoluble in water and soluble in dil aqueous acid and aqueous base.

1.53 g/cm³

202-202.5 °C

479.5°C at 760 mmHg

243.8±29.3 °C

1.704

H2O: <0.1 g/100 mL at 21 ºC

0-6°C

4.22X10-8 mm Hg at 25 deg C (est)

7.2None

Henry's Law constant = 5.85X10-14 atm-cu m/mol at 25 °C (est)

7.2|pKa1 = 2.2; pKa2= 7.24

150.8 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]|148.2 Ų [M+H]+ [CCS Type: TW]|153.81 Ų [M-H]-

Crystals or white powder or granules. Also occurs as the monohydrate and pentahydrate. One gram dissolves in approx 2.5 mL water, in approx 15 mL alc. pH of 1% aq soln 9.35; of 10% soln 10.2. /Sodium salt sesquihydrate/|The microstructure of sulfathiazole crystals obtained by recrystallization at 0, 30, and 70DGC was studied using high resolution transmission electron microscopy. Low magnification electron microscopy study of the crystals showed featureless morphology, yet the resolved lattice images showed imperfections such as dislocations, lattice irregularities and regions of discontinuity.|Several interfacial and partitioning processes were incorporated into a mathematical model describing the in vitro diffusion of drug from a submicron oil-in-water emulsion across a semipermeable membrane. Drug ionization and its effects on charge dependent interfacial, partitioning and mass transport processes are considered. Release studies using sulfathiazole as a test compound were found to be consistent with the model.|X-ray diffraction and infrared spectrophotometric studies were carried out to determine interactions between cellulose acetate phthalate film coatings and either sulfathiazole or sulfathiazole sodium in tablets. A surface interaction was noted when the sodium salt was used.|For more Other Experimental Properties (Complete) data for SULFATHIAZOLE (7 total), please visit the HSDB record page.

May be sensitive to heat, air and light during long-term storage (NTP, 1992). Insoluble in water.

Amines, Phosphines, and Pyridines

SULFATHIAZOLE is an amino acid.

III

6.1(b)

3249

2

36/37/38

26-36

WP2360000

Xi

Stable. Incompatible with strong oxidizing agents.

P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, P501

H315

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Sulfonamide solutions are incompatible with calcium- or other polyionic-containing fluids as well as many other preparations. /Sulfonamides/

A tolerance of 0.1 part per million is established for negligible residues of sulfathiazole in the uncooked edible tissues of swine.|The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies discontinued drug products. Sulfathiazole is included on this list.|The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Sulfathiazole is included on this list.|The following drug products were withdrawn or removed from the market because such drug products or components of such drug products were found to be unsafe or not effective. The following drug products may not be compounded under the exemptions provided by section 503A(a) of the Federal Food, Drug, and Cosmetic Act: All drug products containing sulfathiazole (except those formulated for vaginal use).|New animal drugs for use in animal feeds. Chlortetracycline, sulfathiazole, penicillin. Type A medicated articles: (1) 20 grams of chlortetracycline hydrochloride, 4.4 percent (20 grams) sulfathiazole, and procaine penicillin equivalent to 10 grams of penicillin per pound to No. 046573 in section 510.600(c) of this chapter. (2) 40 grams of chlortetracycline hydrochloride, 8.8 percent (40 grams) sulfathiazole and procaine penicillin equivalent in activity to 20 grams of penicillin per pound to No. 046573 in section 510.600(c) of this chapter. ... Indications for use: For reduction of incidence of cervical abscesses. Treatment of bacterial enteritis (salmonellosis or necrotic enteritis caused by Salmonella choleraesuis and vibrionic dysentery). Maintenance of weight gains in the presence of atrophic rhinitis. Swine 10 pounds of body weight to 6 weeks post-weaning: Increased rate of weight gain and improved feed efficiency. Swine 6 to 16 weeks post-weaning: Increased rate of weight gain. ... Limitations: For swine raised in confinement (dry-lot) or on limited pasture. Feed as sole ration. Withdraw 7 days prior to slaughter.

Anwar J et al; J Pharm Sci 78: 337-342 Apr 1989. Polymorphism of sulfathiazole.|Burger A and RD Dialer; Pharm Acta Helv 58: 72-78 Mar 1983. New investigational results of sulfathiazole polymorphism.|Alpar HD and JA Hersey; Farmaco Ed Prat 34: 532-541 Dec 1979. Effect of suspending agents on the bioavailability of suspensions of sulfathiazole.

Flash point data for this compound are not available, but it is probably combustible. (NTP, 1992)

|Warning|H315 (98.56%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 144 companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Fires involving this compound should be controlled with a dry chemical, carbon dioxide or halon extinguisher. (NTP, 1992)

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should protect this chemical from exposure to light. Keep the container tightly closed under an inert atmosphere, and store under refrigerated temperatures. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

Leachate samples were collected on September 6, 2000, down gradient from the Norman Municipal Landfill research site in central Oklahoma; the landfill was established in the 1920s and closed in 1985(1). Sulfathiazole was tested for but not detected, reporting limit 0.10 ug/L(1). The average concentration in daily flushwater of a US swine confined feeding operation was 971 ug/L assuming 2500 head, average weight of 180 lbs, average administration of 496 mg/day/animal(2). Sulfathiazole was not detected in final effluents of eight wastewater treatment plants in five Canadian cities, sampled in 2002; detection limit 0.004 ug/L(3). The compound has been found up to the low ug/L-level in unspecified sewage samples(4).

Sulfathiazole was not detected in pig urine following prescribed administration, detection limit of 0.01 to 1.6 mg/L, depending on analytical method(1).

Acute oral toxicity (LD50): 4500 mg/kg [Mouse].

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.

LD50 Mouse oral 4500 mg/kg

/AQUATIC SPECIES/ The photocatalytic degradation of sulfacetamide, sulfathiazole, sulfamethoxazole and sulfadiazine in water solutions during their illumination of UV radiation (gmma max 366 nm) with TiO2 catalyst was examined. The growth-inhibition effect of sulfonamides and intermediate products theirs photodegradation was investigated in aqueous solution with the green alga Chlorella vulgaris. The biodegradability of the investigated compounds was determined in the illuminated solutions and is expressed as Biochemical Oxygen Demand. It was found that all of the investigated sulfonamides in the initial solutions were resistant to biodegradation and were toxic relative to C. vulgaris. The toxicity (EC50 values) relative to C. vulgaris increased in the following order sulfacetamide, sulfathiazole, sulfamethoxazole, sulfadiazine. All of the investigated sulfonamides undergo photocatalytic degradation. The toxicity of intermediate products of the sulfonamides degradation was significantly lower than the toxicity of sulfonamides in the initial solutions and was dependent on illumination time and degradation rate. The intermediate products of photocatalysis in contrast to the initial sulfonamides, might be mineralized using biological methods.

Acute hemolytic anemia may occur during the first week of therapy as a result of sensitization or glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. This reaction may also occur in the fetus or premature infant in whom G-6-PD is normally deficient. /Sulfonamides/|Sulfonamides are absorbed from the vaginal mucosa and are distributed into breast milk. Use is not recommended in nursing mothers since sulfonamides may cause hyperbilirubinemia in the infant. In addition, sulfonamides may cause hemolytic anemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient neonates. /Sulfonamides/

Sulfathiazole's production and use as both a human(1) and veterinary antibiotic(2) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), Koc values of 200(2) and 97(3) indicate that sulfathiazole is expected to have moderate to high mobility in soil(SRC). The pKa of sulfathiazole is 7.24(4), indicating that this compound will exist partially in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). Volatilization from moist soil surfaces is not expected to be an important fate process for the neutral species based upon an estimated Henry's Law constant of 5.8X19-14 atm-cu m/mole(SRC), using a fragment constant estimation method(6). Sulfathiazole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.2X10-8 mm Hg(SRC), determined from a fragment constant method(7). In general, sulfonamide antimicrobials are not readily biodegraded and persist in soils(8).|AQUATIC FATE: Based on a classification scheme(1), Koc values of 200(2) and 97(3) indicate that sulfathiazole is not expected to adsorb to suspended solids and sediment(SRC). The Henry's Law constant for the neutral species of sulfathiazole is estimated as 5.8X10-14 atm-cu m/mole(SRC) using a fragment constant estimation method(4). This Henry's Law constant indicates that the neutral species is expected to be essentially nonvolatile from water surfaces(5). A pKa of 7.2(6) indicates sulfathiazole will exist partially in the anion form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(7). Volatilization from water surfaces is not expected to be an important fate process for the neutral species based upon an estimated Henry's Law constant of 5.8X19-14 atm-cu m/mole(SRC), developed using a fragment constant estimation method(8). According to a classification scheme(9), an estimated BCF of 3(SRC), from an estimated log Kow of 0.05(10) and a regression-derived equation(11), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Sulfathaizole is expected to be readily photodegraded in most natural waters as the anionic form is most susceptible to direct photodegradation(6). A biodegradation rate in soil of 50 kg/wk as part of a land treatment study(12) suggests that biodegradation is not an important environmental fate process in water(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), sulfathiazole, which has an estimated vapor pressure of 4.2X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase sulfathiazole is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 7 hrs(SRC), calculated from its rate constant of 5.4X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase sulfathiazole may be removed from the air by wet or dry deposition(SRC). Sulfathiazole contains chromophores that absorb at wavelengths >290 nm(4) and therefore may be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of sulfathiazole with photochemically-produced hydroxyl radicals has been estimated as 5.4X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 7 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Sulfathiazole is not expected to undergo hydrolysis in the environment since amphoteric sulfonamides behave as weak acids and are much more soluble in alkaline than acidic environments(4); they form salts in strongly acid or basic solutions(3). Sulfathiazole is expected to be readily photodegraded in most natural waters as the anionic form is most susceptible to direct photodegradation. In aqueous solution, direct photolysis rates were reported as 2.3X10-5/sec (pH 2.5); 2.3X10-5/sec (pH 3.9); 2.5X10-5/sec (pH 4.9); 5.7X10-5/sec (pH 6.3); 13X10-5/sec (pH 8.4), resulting in sulfanilic acid(5). Sulfathiazole does contain chromophores that absorb at wavelengths >290 nm(2) and therefore may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3 was calculated in fish for sulfathiazole(SRC), using a log Kow of 0.05(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

A Koc of 200 (Kd 4.9) has been reported for sulfathiazole using a loamy sand soil with a pH of 5.2(1). A Koc of 97 was reported using a clay loam soil (pH 6.0, organic content 3.1%)(2). According to a classification scheme(3), these Koc values suggests that sulfathiazole is expected to have moderate to high mobility in soil. The pKa values of sulfathiazole are 2.2 and 7.2(4), indicating that this compound will exist partially in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). However, aromatic amines are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group(6,7), suggesting that mobility may be much lower in some soils(SRC). Treated waste water effluent containing sulfathiazole was applied to soil columns over 23 days; the compound was not detected (detection limit 0.05 ug/L) in the drainage samples(8).

The Henry's Law constant for the neutral species of sulfathiazole is estimated as 5.8X10-14 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that the neutral species is expected to be essentially nonvolatile from water surfaces(2). The pKa values of 2.2 and 7.2(3) indicates sulfathiazole will exist partially in the anion form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(4). Sulfathiazole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.2X10-8 mm Hg(SRC), determined from a fragment constant method(5).

SURFACE WATER: Sulfathiazole was not detected in 139 US streams sampled from 1999-2000, detection limit of 0.05 ug/L(1). It was not detected in 76 water samples collected during 2001 from upstream and downstream of select towns and cities in Iowa during high-, normal-, and low-flow conditions, detection limit 0.05 ug/L(2). Sulfathiazole was not detected in 12 stream and raw water samples collected in a heavily populated, highly urbanized US drainage basin during November and December 2001, reporting level of 0.10 ug/L(3). The compound has been found up to the low ug/L-level in surface water samples(4).

Sulfathiazole residues were tested for in 2,363 farm and fish samples on the market from 1994 to 1998 in Slovenia(1). Sulfonamides were not detected in 99.37% of samples (detection limit = 0.01 mg/kg); no residues were found in poultry samples and half of the positive samples belong to pig tissues(1). Sulfathiazole was detected in one unspecified sample at a concentration between 10 and 50 ng/g wet weight(1).

Because sulfonamides are distributed into milk, and because of the potential for serious adverse reactions from the drugs in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the woman. Because of the risk of kernicterus in infants younger than 2 months of age, use of sulfonamides is contraindicated in lactating women who are nursing such infants. /Sulfonamides/

NIOSH (NOES Survey 1981-1983) has statistically estimated that 3,171 workers (1,476 of these were female) were potentially exposed to sulfathiazole in the US(1). Occupational exposure to sulfathiazole may occur through inhalation and dermal contact with this compound at workplaces where sulfathiazole is produced or used. Use data indicate that the general population may be exposed to sulfathiazole via dermal contact and administration of pharmaceutical products containing sulfathiazole(SRC).

Sulfathiazole is effective against a wide range of gram positive and gram negative pathogenic microorganisms. Although no longer used in humans, it is used in cattle.

Sulfathiazole has known transformation products that include N4-Acetylsulfathiazole.

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.

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.

Both chromosomal and R-factor-mediated resistance to sulfonamides have been attributed to altered forms of dihydropterate synthetase (for which sulfonamides have a lowered affinity). Another mechanism of resistance is the overproduction of PABA, which overcomes the metabolic block imposed by the inhibition of dihydropterate synthetase. Cross-resistance between sulfonamides is the general rule. Resistance does emerge gradually and is widespread in many animal populations; continued use of sulfonamides increases the incidence. Plasmid-mediated sulfonamide resistance in intestinal gram-negative bacteria is often linked with ampicillin and tetracycline resistance.

Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection. (See all compounds classified as Anti-Infective Agents.)

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.

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.

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...

Sulfonamides are usually bacteriostatic in action. Sulfonamides interfere with the utilization of p-aminobenzoic acid (PABA) in the biosynthesis of tetrahydrofolic acid (the reduced form of folic acid) cofactors in susceptible bacteria. Sulfonamides are structural analogs of PABA and appear to interfere with PABA utilization by competitively inhibiting the enzyme dihydropteroate synthase, which catalyzes the formation of dihydropteroic acid (a precursor of tetrahydrofolic acid) from PABA and pteridine; however, other mechanism(s) affecting the biosynthetic pathway also may be involved. Compounds such as pyrimethamine and trimethoprim, which block later stages in the synthesis of folic acid, act synergistically with sulfonamides. Only microorganisms that synthesize their own folic acid are inhibited by sulfonamides; animal cells and bacteria which are capable of utilizing folic acid precursors or preformed folic acid are not affected by these drugs. The antibacterial activity of the sulfonamides is reportedly decreased in the presence of blood or purulent body exudates. /Sulfonamides/|The sulfonamides are structural analogs of para-aminobenzoic acid (PABA) and competitively inhibit an enzymatic step (dihydropterate synthetase) during which PABA is incorporated into the synthesis of dihydrofolic acid (folic acid). Because dihydrofolate synthesis is reduced, the levels of tetrahydrofolate (folinic acid) formed from dihydrofolate diminish. Tetrahydrofolate is an essential component of the coenzymes responsible for single carbon metabolism in cells. Acting as antimetabolites to PABA, sulfonamides eventually block, in a complex fashion, several enzymes. These enzymes include those needed for the biogenesis of purine bases; for the transfer of desoxyuridine to thymidine; and for the biosynthesis of methionine, glycine, and formylmethionyl-transfer-RNA. This results in suppression of protein synthesis, impairment of metabolic processes, and inhibition of growth and multiplication of those organisms that cannot use preformed folate. The effect is bacteriostatic, although a bactericidal action is evident at the high concentrations that may be found in urine.

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. If symptoms (such as redness or irritation) develop, immediately transport the victim to a hospital. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

Maintain an open airway and assist ventilation if necessary. Treat coma, seizures, hypotension, anaphylaxis, and hemolysis if they occur. Replace fluid losses resulting from gastroenteritis with intravenous crystalloids. Maintain steady urine flow with fluids to alleviate crystalluria ... Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. Most antibiotics are excreted unchanged in the urine, so maintenance of adequate urine flow is important. The role of forced diuresis is unclear. Hemodialysis is not usually indicated, except perhaps in patients with renal dysfunction and a high level of a toxic agent. /Antibacterial agents/

/SIGNS AND SYMPTOMS/ 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/|/EPIDEMIOLOGY STUDIES/ In the Collaborative Perinatal Project, the frequency of congenital anomalies was no greater than expected among children of 100 women who were treated with sulfathiazole during the first four lunar months of pregnancy or among the children of 124 women treated with this drug anytime in pregnancy.

4-amino-N-2-thiazolyl Benzenesulfonamide

Formosulfathiazole, formaldehyde-sulfathiazole, Forbina, formo-Cibazol, Socatil. Contains approx 11% formaldehyde. /Polymer with formaldehyde/|Soluble sulfathiazole /Sodium salt sesquihydrate/

Benzenesulfonamide, 4-amino-N-2-thiazolyl-: ACTIVE|SHIGELLA & E COLI ISOLATED SIMULTANEOUSLY FROM DYSENTERY PATIENT SHOWED HIGH RESISTANCE TO SULFATHIAZOLE.|FORMS A SOLUBLE SODIUM SALT /MONOSODIUM 2-SULFANILAMIDOTHIAZOLE; SOLUBLE SULFATHIAZOLE/.|...among the most widely used antibacterial agents in veterinary medicine, chiefly because of low cost and relative efficacy in some common bacterial diseases /Sulfonamides/

THIN-LAYER CHROMATOGRAPHY WAS USED FOR THE SEPARATION OF A SERIES OF SULFONAMIDES.|SULFATHIAZOLE WAS CONVERTED TO THE DIAZONIUM SALT, COUPLED WITH 8-HYDROXYQUINOLINE-5-SULFONIC ACID, & ASSAYED SPECTROPHOTOMETRICALLY @ 530 NM.|GAS-LIQUID CHROMATOGRAPHIC DETERMINATION OF SULFATHIAZOLE, SULFAMERAZINE, SULFAMETHAZINE, & SULFAQUINOXALINE IN FINISHED FEEDS AT LEVELS FROM 0.002-0.05%.|Analyte: sulfathiazole; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards|For more Analytic Laboratory Methods (Complete) data for SULFATHIAZOLE (28 total), please visit the HSDB record page.

HPLC METHOD FOR THE SEPARATION & QUANTITATIVE DETERMINATION OF SULFATHIAZOLE IN PURE SOLN AS WELL AS IN CATTLE URINE.|A SIMPLE HIGH-PRESSURE LIQ CHROMATOGRAPHY FOR THE DETECTION OF SULFATHIAZOLE IN PLASMA & URINE.|GAS-LIQUID CHROMATOGRAPHY AND SPECTROPHOTOMETRY WERE USED FOR THE DETERMINATION OF FIVE SULFONAMIDES. SULFATHIAZOLE WAS RECOVERED FROM LIVER, KIDNEY & MUSCLE AT LEVEL OF 0.1 PPM.|Analyte: sulfathiazole; matrix: milk; procedure: capillary zone electrophoresis with ultraviolet detection at 214 and 254 nm|For more Clinical Laboratory Methods (Complete) data for SULFATHIAZOLE (17 total), please visit the HSDB record page.

Veterinary Drug -> ANTIMICROBIAL_AGENT; -> JECFA Functional Classes|Pharmaceuticals|Pharmaceuticals -> Antiinfectives for systemic use -> Antibiotics and chemotherapeutics for dermatological use -> Chemotherapeutics for topical use -> Sulfonamides -> Antibiotics

Veterinary Drug -> ANTIMICROBIAL_AGENT;