Grundinformationen
- Standard-SMILES
Nc1ccc(S(=O)(=O)Nc2nccs2)cc1- InChIKey
JNMRHUJNCSQMMB-UHFFFAOYSA-N- Summenformel
- C9H9N3O2S2
- Durchschnittliche Molmasse
- 255,3 g/mol
- Monoisotopische Masse
- 255,01361853
Überblick
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.
Namen und Bezeichner
- Bevorzugter Name
- Sulfathiazole
- IUPAC
- 4-amino-N-(1,3-thiazol-2-yl)benzenesulfonamide
- Lokaler Name
- Sulfathiazol
- Englischer Name
- Sulfathiazole
- Summenformel
- C9H9N3O2S2
- Molmasse
- 255.32
Namen und Synonyme
Weitere Namen anzeigen
Datenbank-Bezeichner
- CAS
72-14-0- PubChem CID
- 5340
- DTXSID
DTXSID8026068- ChEMBL
CHEMBL437- ChEBI
CHEBI:9337- UNII
- Y7FKS2XWQH
- EC Number
- 200-771-5
- Nikkaji
- J1.425G
Eigenschaften
Berechnete Struktureigenschaften
- XLogP
- 0,1
- Polarare Oberfläche (TPSA)
- 122 Ų
- H-Brücken-Donoren
- 2
- H-Brücken-Akzeptoren
- 6
- Frei drehbare Bindungen
- 3
- Schwere Atome
- 16
- Formalladung
- 0
- Komplexität
- 320
Experimentelle und physikochemische Eigenschaften
Drugs
Pharmaceuticals -> Antibiotics
Pharmaceuticals -> Antibiotics (Sulfonamide)
Pharmaceuticals -> Listed in ZINC15
LogP
log Kow = 0.05
0.05
0.43
Color/Form
Brown plates, rods or powder from 45% alcohol
Yellowish-white prismatic rods and six sided plates and prisms
Solubility
Insoluble (<1 mg/ml at 70 °F) (NTP, 1992)
Amorphous powder. Practically insol in water /Polymer with formaldehyde/
Soly at 26 °C (mg/100 mL): water 60 (pH 6.03); alcohol 525. Sol in acetone, dil mineral acids, KOH and NaOH solns, ammonia water. Sparingly soluble in ethanol. Practically insoluble in chloroform, ether.
Slightly soluble in dimethyl sulfoxide.
In water, 373 mg/L at 25 °C
Melting Point
396.5 °F (Form I); 347 °F (Form II) (NTP, 1992)
175 °C (form a); 202 °C (form b)
189 °C
Physical Description
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.
White solid; [HSDB]
Solid
Stability/Shelf Life
The stability of sulfamethazine (sulfadimidine) sulfathiazole, sulfameter (sulfamethoxydiazine), and sulfacetamide during acid hydrolysis in one mol/L of hydrochloric acid under increased temperature was examined using high pressure liquid chromatography. Kinetic characteristics of the process of decomposition were calculated from the found values of the concentration of undecomposed sulfonamide in relation to time. The calculated values of activation energy for the individual sulfonamides are given. The paper stresses the illustrativeness of HPLC in the examination of decomposition products.
Physikochemische Eigenschaften
- Schmelzpunkt
- 200 · 200-202 °C (lit.)
- Siedepunkt
- 479.5 · 479.5±47.0 °C(Predicted)
- Dichte
- 1.4629 · 1.4629 (rough estimate)
- Brechungsindex
- 1.656 · 1.6560 (estimate)
- storage temp.
- 2 · 2-8°C
- Löslichkeit
- 0.5 g/l · 0.5g/l
- pka
- 7.2 · 7.2(at 25℃)
- Aggregatzustand
- Solid
- Farbe
- White
- Wasserlöslichkeit
- Insoluble (<0.1 g/100 mL at 21 ºC)
- Merck
- 14 · 14,8943
- BRN
- 226178 · 226178
- Henry's Law Constant
- 1.7 · 1.7×108 mol/(m3Pa) at 25℃, HSDB (2015)
- Stabilität
- Stable. Incompatible with strong oxidizing agents.
- Major Application
- clinical testing
- 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)
- InChIKey
- JNMRHUJNCSQMMB-UHFFFAOYSA-N
- SMILES
- Nc1ccc(cc1)S(=O)(=O)Nc2nccs2
- CAS Datenbank
- 72 · 72-14-0(CAS DataBase Reference)
- NIST chemische Informationen
- Sulfathiazole(72-14-0)
- EPA chemische Informationen
- Sulfathiazole (72-14-0)
Sicherheit und Regulatorisches
GHS-Klassifizierung
GHS Classification
This chemical does not meet GHS hazard criteria for 5.8% (5 of 86) of reports.
Warning
H315 (91.9%): Causes skin irritation [Warning Skin corrosion/irritation]
P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)
Aggregated GHS information provided per 86 reports by companies from 12 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
Gefahrenhinweise
FDA Requirements
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.
Special Reports
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.
History and Incidents
The beginning of modern standards for good manufacturing practices can be traced to an incident that began in December 1940, when the Winthrop Chemical Company of New York put on the market sulfathiazole tablets contaminated with phenobarbital. Hundreds of deaths and injuries resulted. FDA's investigation into Winthrop's sulfathiazole production and the agency's efforts to retrieve the Winthrop drug remaining on the market revealed numerous control deficiencies in the plant and serious irregularities in the firm's attempt to recall the tainted tablets. The incident prompted FDA to require detailed controls in sulfathiazole production at Winthrop and throughout the industry, an approach that became the basis for production control standards for all pharmaceuticals.
Sicherheit und Schutzausrüstung
First Aid
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.
Nonfire Spill Response
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.
Disposal Methods
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.
Personal Protective Equipment (PPE)
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)
Toxikologische Informationen
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.
Environmental Fate
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).
Food Survey Values
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).
Milk Concentrations
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/
Ecotoxicity Excerpts
/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.
Ongoing Test Status
The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=72-14-0][Available from: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=72-14-0]
Effluent Concentrations
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).
Soil Adsorption/Mobility
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).
Human Toxicity Excerpts
/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.
Environmental Biodegradation
AEROBIC: A biodegradation rate of 50 kg/wk was reported following the addition of 10,000 ppm added to soil, as part of an analysis of land treatment capacity for effective biodegradation of waste effluent(1). This rate was slow to moderate in comparison to other organo-sulfur compounds tested, the most rapid being sodium-taurocholate at 950 kg/wk and the slowest being sodium-diethyldithiocarbamate at 10 kt/wk(1). Biodegradation of organic sulfur compounds may result in lower soil pH as a result of sulfur mineralization(1). In general, sulfonamide antimicrobials are not readily biodegraded and persist in soils(2).
Regulatorische Informationen
FDA Requirements
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.
Sicherheitsdaten
- wgk
- 2
- tsca
- TSCA listed
- ridadr
- 3249
- hs_code
- 29350090
- RTECS-Nr.
- WP2360000
- risk_code
- 36/37/38
- hazard_code
- Xi
- safety_code
- 26-36
- hazard_class
- 6.1(b)
- packing_group
- III
- Speicherklasse
- 11 - Combustible Solids
- Giftige Stoffe Daten
- 72-14-0(Hazardous Substances Data)
- Hazard Classifications
- Aquatic Chronic 3Eye Irrit. 2Skin Irrit. 2STOT SE 3
Chemie und Industrie
Pharmakologische Informationen
ATC Code
D06BA02
J - Antiinfectives for systemic use
D - Dermatologicals
QJ - Antiinfectives for systemic use
QD - Dermatologicals
Mechanism of Action
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.
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...
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.
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.
Verwendung und Herstellung
Uses
Antibiotic; [HSDB]
THERAP CAT (VET): Antibacterial
THERAP CAT: Antibacterial
MEDICATION (VET)
MEDICATION
Intrauterine use in cows /Polymer with formaldehyde/
Formulations/Preparations
Formosulfathiazole, formaldehyde-sulfathiazole, Forbina, formo-Cibazol, Socatil. Contains approx 11% formaldehyde. /Polymer with formaldehyde/
Soluble sulfathiazole /Sodium salt sesquihydrate/
Use Classification
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
General Manufacturing Information
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/
Anwendungen
VerwendenSulfonamide antibacterial.
Vor- und nachgelagerte Produkte
Nachgelagerte Produkte
Anbieter50 Anbieter
Ergänzende Hinweise
DefinitionChEBI: A 1,3-thiazole compound having a 4-aminobenzenesulfonamido group at the 2-position.
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