Pharmacokinetic Properties


Sulfonamides are usually given orally, although the soluble sodium salts can be given parenterally, a route that is infrequently used. Except for compounds designed for local gut effects, the sulfonamides are rapidly absorbed from the intestinal tract, primarily from the small intestine. They can usually be found in serum and urine within 30 minutes after ingestion. Peak serum levels are obtained in 2 to 6 hours; urine levels can reach above 500 ^g/mL. Although absorption can occur via other routes (e.g., burned and/or abraded skin, stomach), the amounts absorbed are usually low and unpredictable. A burn area larger than 20% of total body surface can absorb enough drug to result in toxicity, especially if accompanied by renal dysfunction.


Systemically absorbed sulfonamides readily distribute throughout body fluids. They pass the placental barrier and enter the cerebrospinal fluid (CSF) even in the absence of inflammation. The degree of protein binding, the half-life, and the drug's solubility in urine will vary considerably from one sulfonamide to another. Half-lives range from 2.5 to 17 hours, the latter exhibited by sulfadiazine. Sulfadiazine and sulfacetamide tend to have lower protein binding (about 20-30%) than the other major systemic sulfonamides, whose binding ranges from 80 to 90% (e.g., sulfamethoxazole, sulfisox-azole). The effects of high protein binding by a sulfon-amide become almost negligible in body fluids with a paucity of protein (e.g., synovial, peritoneal, ocular); thus, the drug in these sites is primarily in the active unbound form. Most drugs with protein binding above 30% do not cross the placenta; while this reduces toxic potential, it concomitantly lowers drug antibacterial activity.

Metabolism and Excretion

The sulfonamides are degraded in the liver by acetyla-tion and oxidation; metabolites have reduced bacteriological activity. The parent compound and the metabolites are excreted in the urine, primarily by glomerular filtration followed by tubular reabsorption. Some sul-fonamides exhibit diurnal variations in excretion, being three times greater at night than during the day.

Clinical Uses

Sulfonamides have a long record of successful use in the treatment of a wide range of both gram-positive and gram-negative bacterial infections. They are also active against some of the less frequently encountered infections, such as leprosy, malaria, toxoplasmosis, and nocardiosis. Current indications are more limited, especially to the treatment of urinary tract and ear infections, because of frequently encountered resistance and the availability of better and safer agents for infections such as shigellosis, salmonellosis, and meningococcal meningitis. In contrast, the growth of rickettsial organisms is actually stimulated.

Acute uncomplicated urinary tract infections caused by E. coli and other pathogens generally respond promptly to one of the short-acting sulfonamides. Recurrent urinary tract infections (UTIs), when related to some structural abnormality in the tract, are frequently caused by sulfonamide-resistant bacteria.

Sulfadiazine and sulfisoxazole still play a useful role in the prophylaxis of group A streptococcal infections in patients with rheumatic fever who are hypersensitive to penicillin. This is tempered with the potential for toxic-ity and infection with resistant Streptococcus pyogenes.

Trisulfapyrimidine (a combination of sulfadiazine, sulfamerazine, and sulfamethazine), trimethoprim-sulfamethoxazole, or sulfisoxazole can be used as an alternative drug for the treatment of melioidosis caused by Pseudomonas pseudomallei and for infections produced by Nocardia spp.

A number of infections caused by Chlamydia trachomatis, such as trachoma, inclusion conjunctivitis, pneumonia, and urethritis, can be treated with topical or systemic sulfonamides, although tetracycline or erythro-mycin is preferred.

Sulfonamides, such as sulfadiazine, in combination with pyrimethamine, are considered the treatment of choice of symptomatic toxoplasmosis. Patients should be well hydrated to prevent crystalluria; this problem may be reduced with the use of triple sulfas (trisulfapyrimi-dine). Some regimens have included a sulfonamide (sul-fadoxine) in combination with pyrimethamine (Fansidar) for the treatment of chloroquine-resistant malaria caused by P. falciparum.

Topically active sulfonamides are useful in preventing infections in burn patients. Mafenide acetate

(Sulfamylon Cream), the most widely used compound, is effective against P. aeruginosa, an organism that frequently colonizes burns. It is less effective against staphylococci, which also colonize burns. Local absorption of the acetate preparation, which is acidic, can result in respiratory alkalosis. Silver sulfadiazine in a 1% cream can be used as an alternative to mafenide and has good activity against gram-negative bacteria.

Sulfacetamide is used topically for treatment of ocular infections.

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