Pharmacokinetics, metabolism and renal excretion of sulfatroxazole and its 5‐hydroxy‐ and N4‐acetylmetabolites in man

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Abstract
Hydroxylation is the predominant pathway of metabolism for sulfatroxazole in the body, accounting for 70 per cent of the dose. Fifteen per cent of the dose is acetylated unimodally and 10 per cent is excreted unchanged. The half‐lives of sulfatroxazole and its metabolites 5‐hydroxysulfatroxazole and N4‐acetylsulfatroxazole are approximately 22 h after administration of sulfatroxazole. N4‐acetylsulfatroxazole, taken as parent drug, is eliminated by renal excretion (92 per cent of the dose). The initial elimination half‐life of N4‐acetylsulfatroxazole is 4.5 h, which later increases to 70 h as the result of the acetylation‐deacetylation equilibrium. Probenecid inhibits the renal excretion of the metabolites 5‐hydroxy‐ and N4‐acetylsulfatroxazole. Inhibition of the N4‐acetylmetabolite favours the deacetylation, which results in an increase of the T1/2 of sulfatroxazole from 20 to 30 h. The protein binding value of sulfatroxazole is 84 per cent, that of N4‐acetylsulfatroxazole is 37 per cent. Sulfatroxazole is excreted renally by passive processes, while the metabolites are excreted by both passive and active processes.