Sulfisoxazole Acetyl

Pharmaceuticals -> Antibiotics

Pharmaceuticals -> Listed in ZINC15

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

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 <i>p</i>-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.

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.

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.

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 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.

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.

The clearance of sulfisoxazole is 18.7 +/- 3.9 ml/min for total drug and 232 +/- 64 ml/min for the unbound drug.