Half-life sulfonamides

Sulfasalazine is absorbed in the proximal intestine and is then excreted unchanged in the bile. In consequence most of orally administred sulfasalzine reaches the colon as such. It is then split by the intestinal flora into its components sulfapyridine, a sulfonamide antimicrobial agent, and 5-aminosalicylic acid (5-ASA). It has been proven that in inflammatory bowel disease 5-ASA is responsible for the beneficial effects while the sulpha component only contributes to the adverse reaction profile. Although some 5-ASA is absorbed and excreted in urine with a half-life of 0.5-1.5 hours, most is eliminated unchanged in the faeces. Sulfapyridine is to a major extend reabsorbed, metabolized in the liver and excreted in the urine with a half-life, depending on the acetylator phenotype, between 5 and 15 hours. 

The short-acting sulfonamides include sulfadimidine, sulfamerazine and sulfathiazole. Sulfadimidine, as the most important representative of this group, is relatively soluble and has therefore a lower risk of causing crystalluria while sulfamerazine and sulfathiazole are less soluble sulfonamides. Sulfadimidine has good oral absorption. It has an elimination half-life between 1.5 and 5 hours, depending on acetylator phenotype. 

Intermediate-acting sulfonamides include sulfadiazine and sulfamethoxazole. Sulfamethoxazole is combined with trimethoprim in co-trimoxazole. Sulfadiazine shows good penetration into the cerebrospinal fluid and is effective for cerebral Toxoplasmosis. It has an elimination half-life 10-17 hours which prolonged in renal impairment. 

Tolbutamide is well absorbed but rapidly metabolized in the liver. Its duration of effect is relatively short, with an elimination half-life of 4-5 hours, and it is best administered in divided doses. Because of its short half-life, it is the safest sulfonylurea for elderly diabetics. Prolonged hypoglycemia has been reported rarely, mostly in patients receiving certain drugs (eg, dicumarol, phenylbutazone, some sulfonamides) that inhibit the metabolism of tolbutamide. 

Sulfadiazine is a relatively short-acting sulfonamide with an elimination half-life of about 3 h in cattle. The importance of this drug for control of furunculoses in fish is determined by its combined use with the potentiator trimethoprim. 

Hypoglycemia, often during the first hours of combining the two drugs, is the result of an important interaction between sulfonylureas and sulfonamides (184—187). For example, the half-life of tolbutamide was increased from 9.5 to 29 hours by chronic sulfaphenazole and from 9.2 to 26 hours by a single dose of sulfaphenazole (188). Interference by sulfonamides with the protein binding of sulfonylureas may contribute. 

Figure 2.7 N-lsopropyl-thiadiazolyl sulfanilamide (IPTD) 19 was the first sulfonamide that showed antidiabetic properties in the clinics. Carbutamide 20 and tolbutamide 21 are also antidiabetics tolbutamide 21 has a shorter biological half-life than carbutamide 20, due to its methyl group instead of the chlorine atom in addition, tolbutamide does not show antibacterial activity. Glibendamide 22 is an antidiabetic drug with improved therapeutic properties.

A close structural analog of the non-selective COX inhibitor diclofenac, lumiracoxib displays a 500-fold greater selectivity for COX-2 than COX-1 in vivo and exhibits a unique pharmacologic profile that includes rapid absorbance and a relatively short plasma half-life (41, 42). Lumiracoxib lacks the tricyclic structure of the diarylheterocycle class of COX-2 selective inhibitors (e.g., celecoxib and rofecoxib) and does not contain a sulfonamide or sulfone group. Although structurally related, lumiracoxib and diclofenac exhibit large differences in the selectivity of COX-2 inhibition, and the molecular basis for this... 

Sulfisoxazole, USP. 4-Amino-A/-(3.4-dimelhyl-5-isox-azolyDbenzcncsuIfunamidc A/ -(3.4-dinie(hyl-S-isoxa/oIyl) xulfanilamide S-suirunilamido3.4-dimelhylisoxazolc. Sul-n.soxa/ole s plasma half-life is 6 hours. Tliis compound is a while, (xlorlcss, slightly biller, crystalline powder. Its pK, is 3.0. At pH 6 this sulfonamide has a water solubility of 330 mg in 100 mL, and its acciyl derivative has a. solubility of 110 mg in 100 mL of water. 

Trade names Anitrim Apo-Sulfatrim Bactelan Bactrim (GSK) Batrizol Cotrim Ectaprim Esteprim Isobac Pro-Trin Roubac Septra (Monarch) Sulfatrim Trimzol Trisulfa Indications Various infections caused by susceptible organisms Category Antibiotic, sulfonamide Half-life 6-10 hours... 

Trade name Sulfamylon Indications Second- and third-degree burns Category Antiseptic Sulfonamide Half-life N/A... 

Category Antibiotic, sulfonamide Half-life 7-13 hours... 

Category Antibiotic, sulfonamide Antimalarial Half-life 5-8 days... 

Indications Various infections caused by susceptible organisms Category Antibiotic, sulfonamide Folic acid antagonist Half-life 7-12 hours... 

Indications Antiretroviral treatment of HIV-1 Category Protease inhibitor, HIV Sulfonamide Half-life 4.8-6.0 hours... 

Drugs are absorbed, transported, metabolized and excreted sensitization must occur along the way. Information about physical chemistry and biological fate of drugs is generally available. We have abundant data, for example, about solubility, ionization, half-life, protein binding, metabolic handling and mode of excretion of sulfonamides >5>0 moreover, there is no doubt that sulfonamides are able to sensitize. ... 

A short half-life, for instance, does not prevent sensitization since sulfanilamide (which is readily absorbed and excreted) and sulfathlazole (which has the shortest half-life of all sulfonamides) produce the largest number of reactions. On the surface, it seems difficult to reconcile this fact with Lehr s view that the incidence of sensitization depends on the amount and concentration of the sulfa diTig to which patients are exposed but we shall return to a possible explanation of this discrepancy later on. 

---