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Sulfamethoxazole is rapidly absorbed following oral administration. It exists in the blood as unbound, protein-bound, metabolized and conjugated forms. The metabolism of sulfamethoxazole occurs predominately by N4-acetylation, although the glucuronide conjugate has been identified. The free form is considered to be the therapeutically active form. Approximately 70% of sulfamethoxazole is bound to plasma proteins; of the unbound portion, 80% to 90% is in the nonacetylated form.
Following a single 1-g oral dose in 12 volunteer male subjects, the mean peak plasma concentration of 38 µg/mL of intact sulfamethoxazole was achieved by 2 hours. The mean half-life of sulfamethoxazole is approximately 10 hours. However, patients with severe-ly impaired renal function, as shown by a creatinine clearance of less than 30 mL/minute, exhibit an increase in the half-life of sulfamethoxazole, requiring dosage regimen adjustment.
Sulfamethoxazole is excreted primarily by the kidneys chiefly through glomerular filtration but also through tubular secretion. Urine concentrations of sulfamethoxazole are considerably higher than are the concentrations in blood. Eighty percent to 100% of the dose is excreted in the urine as total sulfamethoxazole, of which 30% is intact drug with the remaining as the N4-acetylated metabolite.
Sulfamethoxazole diffuses into cerebrospinal fluid, with peak concentrations occurring at 8 hours and reaching approximately 14% of simultaneous plasma concentrations. The drug has also been shown to distribute to aqueous humor, vaginal fluid and middle ear fluid; it also passes the placental barrier and is excreted in breast milk.
The systemic sulfonamides are bacteriostatic agents and the spectrum of activity is similar for all. Sulfonamides inhibit bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA). Resistant strains are capable of utilizing folic acid precursors or preformed folic acid.
Last reviewed on RxList: 12/8/2004
This monograph has been modified to include the generic and brand name in many instances.
Additional Gantanol Information
- Gantanol Drug Interactions Center: sulfamethoxazole oral
- Gantanol Side Effects Center
- Gantanol FDA Approved Prescribing Information including Dosage
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