Acetyl sulfisoxazole

Pediazole susp (erythromycin es + sulfisoxazole acetyl) tsp-i q6h. 10 days... 

Sulfisoxazole Acetyl, USP. yV-((4-Aminophenyl).sulfo-nyI)-N-(3,4-dimcthyl-3-isoxa7xilyl)aceuimidc W-(3.4-di-... 

Sulfonamides that have a rapid rate of absorption and elimination. These consist of sulfisoxazole (Gantrisin), sulfamethoxazole (Gantanol), sulfa-cytine (Renoquid), and sulfamethiazole (Thiosul-fil). The highly soluble and recently introduced sulfonamides have shown excellent antibacterial activity and lack, or show a minimal, renal toxicity, which is a problem with the older sulfonamides. In addition, sulfisoxazole acetyl is tasteless and hence is preferred for oral use in children. 

Sulfisoxazole (gantrisin, others) is rapidly absorbed and excreted. Its high solubility eliminates much of the renal toxicity inherent in the use of older sulfonamides. Sulfisoxazole is bound extensively to plasma proteins. From 28% to 35% of sulfisoxazole in the blood and 30% in the urine is in the acetylated form. It has a serum tj of 5-6 hours and 95% of a single dose is excreted by the kidney in 24 hours. Drug concentrations in urine greatly exceed those in blood and may be bactericidal. The CSF concentration is 33% of that in the blood. Sulfisoxazole acetyl is tasteless and hence preferred for oral use in children it is marketed in combination with erydiromycin (PEDIAZOLE, Others) for use in children with otitis media. 

Sulfonamides having a free j )-amino group are readily assayed by titration with nitrous acid. The sulfonamide function may also be titrated with base, such as lithium methoxide. The majority of the sulfas listed in the U.S. Pharmacopeia XXII, however, are assayed by chromatographic methods, particularly high performance liquid chromatography (49). Sulfonamides for which assays are listed in the U.S. Pharmacopeia XXII-National Formulary XVII include the following sulfacetamide, sulfabenzamide, sulfadiazine, sulfadoxine, sulfamerazine, sulfamethazine, sulfamethizole, sulfamethoxazole, sulfapyridine, sulfasalazine, sulfathiazole, sulfinpyrazone, sulfis ox azole, sulfisoxazole acetyl, sulfisoxazole diolamine, sulfoxone, triple sulfa, dapsone, and various combinations with prednisolone, pyrimethamine, and trimethoprim. 

Examples sulfacetamide, sulfafurazole, sulfisoxazole acetyl, sulfacitine, etc. 

Dose 2 to 4 g initially oral, followed by 4 to 8 ga day in 4 to 6 divided doses. C. Sulfisoxazole Acetyl INN, USAN, Acetyl Sulphafurazole BAN,... 

Erythromycin Ethylsuccinate and Sulfisoxazole Acetyl Pediazole MAS Suspending Agent... 

This presumably forms oxime, 120, on reaction with hydroxylamine that intermediate is not isolated as it cyclizes spontaneously to the isoxazole, 121. Acylation of the isoxazole with the sulfonyl chloride, 88, affords sulfisoxazole (98) after removal of the acetyl group. 

Acetic anhydride Acetaminophen Acetazolamide Acetrizoate sodium Acetyl cysteine Acetyl sulfisoxazole Afloqualone... 

Sulfisoxazole Sulfisoxazole, ATi-(3,4-dimethyl-5-isoxazolyl)sulfanilamide (33.1.19), is synthesized by reacting 4-acetylaminobenzenesulfonyl chloride with 5-amino-3, 4-dimethylisoxazol (33.1.17), which is in turn synthesized by heterocyclization of 2-methy-lacetylacetonitrile with hydroxylamine, and subsequent acidic hydrolysis (hydrochloric add) of the protective acetyl group in the resulting product (33.1.18) [18,19]. 

Bekersky I, Colburn WA. Acetylation of sulfisoxazole by the isolated perfused rat kidney. J Pharm Sci 1980 69 1359. 

Acetyl Sulfisoxazole. N-[(4-Amumphenyl)sulfon-y(7-N-(3,4-dimethyl-S-isoxazolyl)acctamlde W-acelyl-N1-(3,4-dimetkyl-5-isoxazolyl)sulfan ila mide IV -monoacetyl sulfisoxazole Gantrisin Acetyl. CjjH.jNjO.S mol wt 309.35. C 50.47%. H 4.89%. N 13.58%. O io.69%, S 10.37%. Prepd by the action of acetic anhydride on Sulfisoxazole sus -pended in acetone and pyridine Hoffer, U.S. pat. 2,721,200 (1955 to Hoffmann-La Roche). 

Sulfamethoxazole is a close congener of sulfisoxazole, but its rates of enteric absorption and urinary excretion are slower it has a serum t of II hours. It is administered orally and employed for both systemic and urinary tract infections. Precautions must be observed to avoid crystalluria because of the high percentage of the acetylated, relatively insoluble form of the drug in urine. 

It is prepared by first converting sulfisoxazole into its sodium salt by treatment with sodium hydroxide and then carrying out the selective acetylation at N with an equimolar quantity of either acetic anhydride or acetyl chloride. 

The acetyl compound is usually split in the intestinal tract and subsequently gets absorbed as sulfisoxazole , i.e., it is a befitting prodrug for sulfisoxazole. 

The orally administered sulfonamides are well absorbed from the gastrointestinal (Gl) tract, distributed fairly widely, and excreted by the kidney. The drugs are bound to plasma protein (sulfisoxazole, 30-70%, sulfamethoxazole, 70%) and, as such, may displace other protein-bound drugs as well as bilirubin. The latter phenomenon disqualifies them for use in late term pregnancy as they can cause neonatal jaundice. Sulfonamides are partly deactivated by acetylation at N-4 and glucuronidation of the anilino nitrogen in the liver. 

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