Acetyl sulfisoxazole API Manufacturers

General Description:

Acetyl sulfisoxazole, identified by CAS number 80-74-0, is a notable compound with significant therapeutic applications. 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:

This drug is primarily indicated for: 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 . Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Acetyl sulfisoxazole undergoes metabolic processing primarily in: 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 . This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Acetyl sulfisoxazole are crucial for its therapeutic efficacy: 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 . The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Acetyl sulfisoxazole is an important consideration for its dosing schedule: The serum half-life is 10 -12 hours . This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Acetyl sulfisoxazole exhibits a strong affinity for binding with plasma proteins: Approximately 85% of a dose of sulfisoxazole is bound to plasma proteins, primarily to albumin; 65% to 72% of the unbound portion is in the nonacetylated form . This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Acetyl sulfisoxazole from the body primarily occurs through: The mean urinary excretion recovery following oral administration of sulfisoxazole is 97% within 48 hours, of which 52% is the parent drug, and the remaining as the N4-acetylated metabolite. It is excreted in human milk . Sulfisoxazole and its acetylated metabolites are excreted primarily by the kidneys through glomerular filtration . Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Acetyl sulfisoxazole is distributed throughout the body with a volume of distribution of: The sulfonamides are widely distributed throughout all body tissues . It readily crosses the placental barrier and enters into fetal circulation and also crosses the blood-brain barrier. In healthy subjects, cerebrospinal fluid concentrations of sulfisoxazole vary; in patients with meningitis, however, concentrations of free drug in cerebrospinal fluid as high as 94 mcg/mL have been reported . In a pharmacokinetic study, the apparent volume of distribution for total drug was 10.9 +/- 2.0 liters and 136 +/- 36 liters for the unbound drug, indicating that sulfisoxazole is primarily distributed extracellularly . This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Acetyl sulfisoxazole is a critical factor in determining its safe and effective dosage: The clearance of sulfisoxazole is 18.7 +/- 3.9 ml/min for total drug and 232 +/- 64 ml/min for the unbound drug . It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Acetyl sulfisoxazole exerts its therapeutic effects through: 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 . The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Acetyl sulfisoxazole functions by: Sulfisoxazole is a competitive inhibitor of the enzyme dihydropteroate synthetase. It inhibits bacterial synthesis of dihydrofolic acid by preventing the condensation of the pteridine with para-aminobenzoic acid (PABA), a substrate of the enzyme dihydropteroate synthetase. The inhibited reaction is necessary in these organisms for the synthesis of folic acid . This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Acetyl sulfisoxazole belongs to the class of organic compounds known as aminobenzenesulfonamides. These are organic compounds containing a benzenesulfonamide moiety with an amine group attached to the benzene ring, classified under the direct parent group Aminobenzenesulfonamides. This compound is a part of the Organic compounds, falling under the Benzenoids superclass, and categorized within the Benzene and substituted derivatives class, specifically within the Benzenesulfonamides subclass.

Categories:

Acetyl sulfisoxazole is categorized under the following therapeutic classes: Amides, Amines, Aniline Compounds, Anti-Bacterial Agents, Cytochrome P-450 CYP2C9 Inhibitors, Cytochrome P-450 CYP2C9 Inhibitors (weak), Cytochrome P-450 Enzyme Inhibitors, Genito Urinary System and Sex Hormones, Gynecological Antiinfectives and Antiseptics, Sulfanilamides, Sulfonamide Antibacterial, Sulfonamides, Sulfones, Sulfur Compounds. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Acetyl sulfisoxazole include:

• Melting Point: 192 - 195