This study assessed the efficacy of pyrimethamine and sulfadiazine in treating mice infected with several atypical Toxoplasma gondii during an acute infection. A total of seven strains of Toxoplasma gondii were injected into Swiss mice. Treatment options for infected mice were pyrimethamine at 3-200 mg/kg per day, sulfadiazine at 10-640 mg/kg per day, or a lower dosage of a combination of the two medications. To assess the relationship between genotype and sensitivity to pyrimethamine and/or sulfadiazine, descriptive analysis was employed. The strains TgCTBr4 and TgCTBr17 (genotype 108) responded less well to pyrimethamine or sulfadiazine therapy. The strains TgCTBr1 and TgCTBr25 (genotype 206) were equally sensitive to PYR, but not to sulfadiazine therapy. The only strain that responds well to treatment with both medications is the TgCTBr9 strain (genotype 11) [1].

Absorption, Distribution and Excretion
Sulfadiazine is primarily excreted in the urine. It has extremely low skin permeability. Absorption is only a concern when used for large-area burns. Metabolisms/Metabolites Known human metabolites of sulfadiazine include sulfadiazine hydroxylamine.

Hepatotoxicity
Like other sulfonamides, sulfadiazine can cause characteristic, specific liver injury, resembling drug allergies or hypersensitivity reactions. The typical onset is a sudden onset of fever and rash within days or weeks of administration, followed by jaundice. The injury pattern is usually mixed, but fatal cases are often hepatocellular, although persistent cholestatic injury has also been reported. Eosinophilia or atypical lymphocytosis are also common, and their clinical presentation can be considered part of drug-induced rash with eosinophilia and systemic symptoms syndrome (DRESS). Sulfadiazine has also been reported to cause Stevens-Johnson syndrome. Sulfonamides, including sulfadiazine, are associated with many cases of acute liver failure, and as a class of drugs, sulfonamides remain one of the top 5 to 10 causes of drug-induced specific fulminant hepatic failure. However, most cases of sulfonamide-induced liver injury resolve rapidly, usually within 2 to 4 weeks, unless cholestasis is severe. Liver damage occurs more rapidly upon re-exposure to sulfonamides, potentially within a day or after re-exposure. Patients with liver injury caused by sulfadiazine may have previously taken the drug without experiencing liver damage. Sulfonamides (such as sulfadiazine) can also cause mild and transient ALT elevations, but do not develop into jaundice or more serious liver damage, whether occurring alone or as part of a systemic hypersensitivity reaction. Sulfonamides are also associated with the formation of hepatic granulomas.

[1]. Kopmann C, et al. Abundance and transferability of antibiotic resistance as related to the fate of sulfadiazine in maize rhizosphere and bulk soil. FEMS Microbiol Ecol. 2013 Jan;83(1):125-34.
[2]. Silva LA, et al. Efficacy of sulfadiazine and pyrimetamine for treatment of experimental toxoplasmosis with strains obtained from human cases of congenital disease in Brazil. Exp Parasitol. 2019 Jul;202:7-14.

Sulfadiazine is a sulfonamide compound composed of a 4-aminobenzenesulfonamide group linked to a pyrimidine ring. It possesses various functions including antibacterial, anti-infective, anticoccal, antiprotozoal, EC 2.5.1.15 (dihydropterolate synthase) inhibitor, EC 1.1.1.153 (pterin reductase (L-erythro-7,8-dihydrobiopterin formation)) inhibitor, xenobiotic, environmental pollutant, and drug allergen. It belongs to the pyrimidine, sulfonamide, substituted aniline, and sulfonamide antibiotic classes. Its functions are related to those of sulfonamide compounds. It is the conjugate acid of sulfadiazine acid. Sulfadiazine is a prescription antibacterial drug approved by the U.S. Food and Drug Administration (FDA) for the prevention and treatment of certain types of bacterial infections, including chancroid, toxoplasmosis encephalitis, urinary tract infections, and other infections. Toxoplasmosis encephalitis may be an opportunistic infection (OI) of HIV.
It is a short-acting sulfonamide drug, often used in combination with pyrimethamine, for the treatment of toxoplasmosis in patients with acquired immunodeficiency syndrome and newborns with congenital infections.
Silver sulfadiazine is a sulfonamide derivative topical antibacterial agent, mainly used for second- and third-degree burns.
Sulfadiazine is a sulfonamide antibacterial drug.
Sulfadiazine is a sulfonamide drug. It is used to treat mild to moderate infections caused by susceptible bacteria. Like other sulfonamides, sulfadiazine is a known cause of clinically significant specific liver injury.
There are reports and relevant data on sulfadiazine in the Chinese honeybee (Apis cerana).
Sulfadiazine is a synthetic pyrimidinyl sulfonamide derivative, belonging to the short-acting bacteriostatic agents. It inhibits bacterial folic acid synthesis by competing with para-aminobenzoic acid. Sulfadiazine is used in combination with pyrimethamine to treat toxoplasmosis in patients with acquired immunodeficiency syndrome and congenital infections in newborns. (NCI04)
Silver sulfadiazine is a topical sulfonamide drug with antibacterial and antifungal activity. Silver sulfadiazine likely works through the combined action of silver and sulfadiazine. When the drug interacts with body fluids containing sodium chloride, silver ions are slowly and continuously released to the wound site. Ionized silver atoms catalyze the formation of disulfide bonds, leading to changes in protein structure and inactivation of thiol-containing enzymes; silver ions can also intercalate into DNA, thereby interfering with bacterial replication and transcription. As a competitive inhibitor of para-aminobenzoic acid (PABA), sulfadiazine inhibits bacterial dihydropteroate synthase, thereby disrupting folic acid metabolism and ultimately leading to inhibited DNA synthesis.
Sulfadiazine is a short-acting sulfonamide drug, often used in combination with pyrimethamine to treat patients with acquired immunodeficiency syndrome and toxoplasmosis in congenitally infected newborns. See also: Silver sulfadiazine (salt form); Sodium sulfadiazine (salt form); Sulfadiazine; Trimethoprim (component)... See more...

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Drug Indications
For the treatment of rheumatic fever and meningococcal meningitis.
Can be used as an adjunct therapy for the prevention and treatment of wound infections in patients with second- and third-degree burns.

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Mechanism of Action
Sulfadiazine is a competitive inhibitor of bacterial dihydropteroate synthase. This enzyme is essential for the proper processing of para-aminobenzoic acid (PABA), which is required for folic acid synthesis. This inhibition is necessary for folic acid synthesis in these microorganisms.
Studies using radioactive microparticle-based silver sulfadiazine, electron microscopy, and biochemical techniques have shown that the mechanism of action of silver sulfadiazine against bacteria differs from that of silver nitrate and sodium sulfadiazine. Silver sulfadiazine acts only on the cell membrane and cell wall, thereby producing a bactericidal effect. The specific mechanism of action is not yet clear, but the effectiveness of silver sulfadiazine may stem from synergistic effects or the combined action of its components. Silver is a biocidal agent that can bind to a variety of targets. Silver ions can bind to nucleophilic amino acids and sulfhydryl, amino, imidazole, phosphate, and carboxyl groups in proteins, leading to protein denaturation and inhibiting enzyme activity. Silver can bind to cell membranes and proteins, causing membrane proton leakage and ultimately cell death. Sulfadiazine is a competitive inhibitor of bacterial para-aminobenzoic acid (PABA), a substrate of dihydropteroate synthase. This reaction is crucial for the synthesis of folic acid by these microorganisms.

C10H10N4O2S

250.276

250.052

68-35-9

Sulfadiazine sodium;547-32-0;Sulfadiazine-d4;1020719-78-1;Sulfadiazine-13C6;1189426-16-1

5215

White to off-white solid powder

1.5±0.1 g/cm3

512.6±52.0 °C at 760 mmHg

253 °C (dec.)(lit.)

263.8±30.7 °C

0.0±1.3 mmHg at 25°C

1.679

-0.12

2

6

3

17

327

0

S(C1C([H])=C([H])C(=C([H])C=1[H])N([H])[H])(N([H])C1=NC([H])=C([H])C([H])=N1)(=O)=O

SEEPANYCNGTZFQ-UHFFFAOYSA-N

InChI=1S/C10H10N4O2S/c11-8-2-4-9(5-3-8)17(15,16)14-10-12-6-1-7-13-10/h1-7H,11H2,(H,12,13,14)

4-amino-N-pyrimidin-2-ylbenzenesulfonamide

RP 2616; RP2616; RP-2616

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 : ≥ 50 mg/mL (~199.78 mM)
H2O : < 0.1 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.99 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 2.5 mg/mL (9.99 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (9.99 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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