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1 Excretion of sulfamethoxazole and trimethoprim is primarily by the kidneys through both glomerular filtration and tubular secretion. These steady-state levels were achieved after three days of drug administration.
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The steady-state mean plasma levels of free and total sulfamethoxazole were 57.4 mcg/mL and 68 mcg/mL, respectively.
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During administration of 800 mg sulfamethoxazole and 160 mg trimethoprim b.i.d., the mean steady-state plasma concentration of trimethoprim was 1.72 mcg/mL. Detectable amounts of sulfamethoxazole and trimethoprim are present in the blood 24 hours after drug administration. However, patients with severely impaired renal function exhibit an increase in the half-lives of both components, requiring dosage regimen adjustment (see DOSAGE AND ADMINISTRATION section). The mean serum half-lives of sulfamethoxazole and trimethoprim are 10 and 8 to 10 hours, respectively. Peak blood levels for the individual components occur 1 to 4 hours after oral administration. The presence of 10 mg percent of sulfamethoxazole in plasma decreases the protein binding of trimethoprim by an insignificant degree trimethoprim does not influence the protein binding of sulfamethoxazole. Approximately 70% of sulfamethoxazole and 44% of trimethoprim are bound to plasma proteins. The free forms of sulfamethoxazole and trimethoprim are considered to be the therapeutically active forms. The principal metabolites of trimethoprim are the 1- and 3-oxides and the 3'- and 4'-hydroxy derivatives. The metabolism of sulfamethoxazole occurs predominately by N 4-acetylation, although the glucuronide conjugate has been identified.
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Both sulfamethoxazole and trimethoprim exist in the blood as unbound, protein-bound and metabolized forms sulfamethoxazole also exists as the conjugated form. Sulfamethoxazole and trimethoprim is rapidly absorbed following oral administration.