Sulfamethazine is an antibacterial sulfonamide. Like other sulfonamides, sulfamethazine is bacteriostatic, competitively inhibiting dihydropteroate synthase to block folate synthesis and inhibit growth and multiplication. Sulfamethazine is metabolized by cytochrome P450 isoforms and arylamine N-acetyltransferase 2 in a sex-dependent manner.
Cremomethazine,MSD,US,1947
Sulfamethazine is an antibacterial.This compound is a contaminant of emerging concern (CECs).
ChEBI: A sulfonamide consisting of pyrimidine with methyl substituents at the 4- and 6-positions and a 4-aminobenzenesulfonamido group at the 2-position.
A flask heated in an oil bath is filled with 600 ml water and 60 g (1 mol)
glacial acetic acid (or an equivalent quantity of diluted acetic acid). While
stirring 235 g (1.1 mols) anhydrous p-aminobenzenesulfonamidoguanidine (or
an equivalent quantity of a nonanhydrous product) and 122 g (1 mol) sodium
acetylacetonate 100% purity (or an equivalent quantity of product of a lower
purity) are introduced into the flask while stirring.
The temperature of the reaction mixture is brought to 102°C to 103°C, the
mixture is further stirred at this temperature during 24 hours. The pH value of
the mixture, which should range between 5 and 6 is checked during the
reaction.
On expiry of the reaction period heating is cut off, the mass being cooled or
allowed to cool down to 60°C.
Filtering under suction is effected, the solids on the filter being washed with
100 ml water at 80°C.
After drying of the product on the filter 256 g of 2-paminobenzenesulfonamido-
4,6-dimethylpyrimidine, melting point 196°C to
197°C, purity 99.5% are obtained. The output is 92% of the theory calculated
with respect to the sodium acetylacetonate employed.
Calfspan Tablets [Veterinary] (Fort Dodge Animal Health); Sulka S Boluses [Veterinary] (Fort Dodge Animal Health); SulfaSURE SR Bolus [Veterinary] (Boehringer Ingelheim Animal Health);Crermomethazine;Deladine;Dimezathine;Hava-span;Intradin;Neotrizine;Rigesol;Rivodin;S-dimidine;Spanbolet;Sulka-s;Sulphamezathine;Sulphfmezatine;Superseptyl;Sustain iii;Tersulpha;Trisulfaminic;Trisulfaminie.
World Health Organization (WHO)
Sulfadimidine, a sulfonamide anti-infective agent, was introduced
in 1942 for the treatment of bacterial infections. The importance of sulfonamides
has subsequently decreased as a result of increasing resistance and their
replacement by antibiotics which are generally more active and less toxic. The
sulfonamides are known to cause serious adverse effects such as renal toxicity,
sometimes fatal exfoliative dermatitis and erythema multiforma and dangerous
adverse reactions affecting blood formation such as agranulocytosis and
haemolytic or aplastic anaemia. Sulfadimidine is still used in some countries as a
injectable or oral antimicrobial for susceptible infections.
This drug is used for pneumococcal, staphylococcal, and streptococcal infections as well
as for sepsis, gonorrhea, and other infectious diseases. Synonyms of this drug are sulfadiamezin and sulfadimidin.
Sulfamethazine’splasma half-life is 7 hours. This compound is similar inchemical properties to sulfamerazine and sulfadiazine butdoes have greater water solubility than either. Its pKa is 7.2.Because it is more soluble in acid urine than sulfamerazineis, the possibility of kidney damage from use of the drug isdecreased. The human body appears to handle the drugunpredictably; hence, there is some disfavor to its use in thiscountry except in combination sulfa therapy (in trisulfapyrimidines,USP) and in veterinary medicine.
Odorless sticky, white or creamy-white crystalline powder. Slightly bitter taste. An antibacterial.
Water solubility increases rapidly with increasing pH [Merck]. Insoluble in water.
Sulfamethazine is sensitive to light and may also be sensitive to heat. The presence of oxygen and moisture may accelerate the effects of heat and light .
Flash point data for Sulfamethazine are not available; however, Sulfamethazine is probably combustible.
Pharmaceutical Applications
2-Sulfanilamido-4,6-methylpyrimidine (syn: sulphamethazine,
sulfamezathine). A water-soluble compound, unstable
on exposure to light. It is usually administered by
mouth and is a component of some triple sulfonamide
combinations.
The spectrum is typical of the group, but sulfadimidine
exhibits relatively low potency. It is well absorbed
after oral administration. It is extensively metabolized,
predominantly
by acetylation. The mean plasma half-life
(1.5–5 h) varies with acetylator status.
In addition to side effects common to the group, a serious
interaction between ciclosporin (cyclosporin A) and sulfadimidine,
leading to reduced ciclosporin levels, has been
reported.
Sulfamethazine is an antimicrobial sulfur drug that blocks the synthesis of dihydrofolic acid by inhibiting the enzyme dihydropteroate synthase. Sulfamethazine is a competitive inhibitor of bacterial para-aminobenzoic acid (PABA), which is required for bacterial synthesis of folic acid. It induces CYP3A4 expression and is acetylated by N-acetyltransferase. It exhibits sex dependent pharmacokinetics, metabolized by the male specific isoform CYP2C11. Sulfamethazine is bacteriostatic.
Moderately toxic by intravenous and intraperitoneal routes. Experimental teratogenic and reproductive effects. Questionable carcinogen with experimental tumorigenic data. When heated to decomposition it emits very toxic fumes of SOx and NOx.
Sulfamethazine, N1
-(4,6-dimethyl-2-pyrimidinyl)sulfanilamide (33.1.13),
is also synthesized in the aforementioned manner by reacting 4-acetylaminobenzenesulfonyl
chloride with 2-amino-4,6-dimethylpyrimidine, which is in turn synthesized by condensing
acetylacetone with guanidine followed by hydrolysis of the acetylamino group using a base.
Crystallise it from dioxane or aqueous dioxane. [Caldwell et al. J Am Chem Soc 63 2188 1941, Roblin et al. J Am Chem Soc 64 567 1942, Beilstein 25 III/IV 2215.]
[1] C J ALLEGRA. Interaction of sulfonamide and sulfone compounds with Toxoplasma gondii dihydropteroate synthase.[J]. Journal of Clinical Investigation, 1990, 85 2: 371-379. DOI:
10.1172/jci114448[2] S A SALMON. Comparison of MICs of ceftiofur and other antimicrobial agents against bacterial pathogens of swine from the United States, Canada, and Denmark.[J]. Journal of Clinical Microbiology, 1995, 33 9: 2435-2444. DOI:
10.1128/jcm.33.9.2435-2444.1995[3] M.J.B. MENGELERS. Structure-activity relationships between antibacterial activities and physicochemical properties of sulfonamides[J]. Journal of veterinary pharmacology and therapeutics, 2003, 20 4: 276-283. DOI:
10.1046/j.1365-2885.1997.00063.x[4] FENG-JIAO PENG. Joint antibacterial activity of soil-adsorbed antibiotics trimethoprim and sulfamethazine[J]. Science of the Total Environment, 2015, 506: Pages 58-65. DOI:
10.1016/j.scitotenv.2014.10.117[5] REBECA LóPEZ-SERNA Damià B Mira Petrovi. Direct analysis of pharmaceuticals, their metabolites and transformation products in environmental waters using on-line TurboFlow chromatography–liquid chromatography–tandem mass spectrometry[J]. Journal of Chromatography A, 2012, 1252: Pages 115-129. DOI:
10.1016/j.chroma.2012.06.078
