SULFISOXAZOLE ACETYL (200 MG)

Absorption

Readily absorbed from the gastrointestinal tract .
In a pharmacokinetic study, the adjustments for variable renal clearances between oral and intravenous administration and using the unbound plasma concentrations, the bioavailability for an oral dose of sulfisoxazole was found to be 0.95 +/- 0.04 .

Toxicity

LD50=6800 mg/kg (Orally in mice) .
Sulfonamide-induced hypersensitivity reactions, although uncommon, can be severe. They can include rare life-threatening cutaneous reactions such as erythema multiform (Stevens-Johnson syndrome) and toxic epidermal necrolysis. Crystalluria may result in dysuria, renal colic, haematuria and acute renal obstruction .
Other infrequent reactions include granulocytopenia, agranulocytosis, aplastic anemia, thrombocytopenic purpura and toxic hepatitis. Rarely, hemolysis may occur in individuals deficient in glucose-6-phosphate dehydrogenase .
The severe or irreversible adverse effects of sulfisoxazole, which give rise to more complications which may include: nephrotoxicity, blood dyscrasias, interstitial nephritis, hematuria, crystalluria, oliguria, anuria, lumbar pain, and tubular necrosis .
The symptomatic adverse reactions produced by sulfisoxazole are more or less tolerable and if severe, may be treated symptomatically, these include anorexia, diarrhea, rashes, pruritus, nausea and vomiting, hypersensitivity reactions, Photosensitivity reactions .
Overdosage: Continuously forced diuresis may be beneficial and an alkaline urine should be initiated .

Originator

Gantrisin Acetyl ,Roche ,US ,1954

The Uses of SULFISOXAZOLE ACETYL (200 MG)

Antibacterial.

The Uses of SULFISOXAZOLE ACETYL (200 MG)

Sulfisoxazole Acetyl is an antibiotic used in the prevention of infection especially when used in conjunction with erythromycin.

Background

Sulfisoxazole acetyl is an ester of sulfisoxazole, a broad-spectrum sulfanilamide and a synthetic analog of para-aminobenzoic acid (PABA) with antibacterial activity. Sulfisoxazole acetyl competes with PABA for the bacterial enzyme, dihydropteroate synthase, preventing the incorporation of PABA into dihydrofolic acid, which is the precursor of folic acid. This process causes an inhibition of bacterial folic acid synthesis and de novo synthesis of purines and pyrimidines, resulting in cell growth arrest and cell death .
It is often combined with erythromycin to treat acute otitis media caused by the bacteria, haemophilus influenzae .

Indications

Acute, recurrent or chronic urinary tract infections (primarily pyelonephritis, pyelitis and cystitis) due to susceptible organisms (usually Escherichia coli, Klebsiella-Enterobacter, staphylococcus, Proteus mirabilis and, less frequently, Proteus vulgaris) in the absence of obstructive uropathy or foreign bodies
Meningococcal meningitis where the organism has been demonstrated to be susceptible. Haemophilus influenzae meningitis as adjunctive therapy with parenteral streptomycin
Meningococcal meningitis prophylaxis .
Acute otitis media due to Haemophilus influenzae when used concomitantly with adequate doses of penicillin or erythromycin (see appropriate labeling for prescribing information) .
Trachoma, inclusion conjunctivitis, nocardiosis, chancroid, toxoplasmosis as adjunctive therapy with pyrimethamine. Malaria due to chloroquine-resistant strains of Plasmodium falciparum, when used as adjunctive therapy .
Currently, the increasing frequency of resistant organisms is a limitation of the usefulness of antibacterial agents including the sulfonamides, especially in the treatment of chronic and recurrent urinary tract infections .

Definition

ChEBI: Sulfisoxazole acetyl is a sulfonamide and a member of benzenes.

Manufacturing Process

267 grams (1 mol) of sulfisoxazole were suspended in 400 ml of acetone and 79 grams (1 mol) of dry pyridine at 20-25°C in a round-bottom flask equipped with a stirrer and thermometer. 132 grams (1 mol) of acetic anhydride were added within 3 minutes with stirring. The sulfisoxazole dissolved in the mixture and a clear solution resulted. The temperature rose to 39-40°C. After stirring for several minutes, the product started to crystallize as a white crystalline mush. The temperature rose to 42-43°C maintained itself at this temperature for 15-30 minutes, and then started to drop. Stirring was continued for 5 hours and the mixture was then allowed to stand for 10 hours. One liter of 2.5-3.0% ice-cold aqueous ammonia and some fresh ice were then added while stirring and the crystals were filtered without delay. The crystals were washed on the filter with 1 liter of ice-cold 1% ammonia and then with 1 liter of water. The material on the filter was well pressed off, washed with 200-300 ml of alcohol and dried at 70°C to constant weight. The N-monoacetyl sulfisoxazole melted at 193-194°C and showed a positive Bratton-Marshall reaction and a positive Hucknall-Turfat reaction.
The product is in the form of colorless crystals which are somewhat water repellent. It is insoluble in alkali but is saponified upon standing in alkaline suspension (3% ammonia). It is soluble in strong acids (20-36% HCl or 10 N H2SO4) and is rapidly saponified upon standing.

brand name

Gantrisin (Roche).

Therapeutic Function

Antimicrobial

General Description

Sulfisoxazole acetyl shares the actions and usesof the parent compound, sulfisoxazole. The acetyl derivativeis tasteless and, therefore, suitable for oral administration, especiallyin liquid preparations. The acetyl compound is splitin the intestinal tract and absorbed as sulfisoxazole; that is, itis a prodrug for sulfisoxazole.

Pharmacokinetics

Sulfisoxazole is a sulfonamide antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with action against most gram-positive and many gram-negative organisms. Many strains of an individual species may be resistant to this drugf. Sulfonamides inhibit the multiplication of bacteria by acting as competitive inhibitors of p-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus .

Metabolism

Sulfisoxazole acetyl is a prodrug of sulfisoxazole. The acetyl group is added to make the drug poorly water-soluble and is hydrolyzed in vivo to the active drug , .
N1-acetyl sulfisoxazole is metabolized to sulfisoxazole by digestive enzymes in the gastrointestinal tract and is absorbed as sulfisoxazole. This enzymatic splitting is thought to be responsible for slower absorption and lower peak blood concentrations are achieved after administration of an equal oral dose of sulfisoxazole. With sustained administration of acetyl sulfisoxazole, blood concentrations approximate those of sulfisoxazole. Following a single 4 gram dose of acetyl sulfisoxazole to healthy volunteers, maximum plasma concentrations of sulfisoxazole ranged from 122 to 282 mcg/mL (mean, 181 mcg/mL) for the pediatric suspension and occurred between 2 and 6 hours postadministration of sulfisoxazole, in a pharmacokinetic study .