AbstractIntestinal bypass surgery in 4 morbidly obese females (110‐150 kg) had no permanent effect on the rate or amount of sulfisoxazole absorption. The loss of weight up to 44 per cent within an individual over a year's time had no significant effect on the apparent volumes of distribution or other pharmacokinetic parameters of sulfisoxazole and its N4‐ acetylsulfisoxazole metabolite. Dosing of this drug on a mgkg− 1basis is contraindicated. Renal clearances of sulfisoxazole were reasonably constant within a study but those of the N4‐acetylsulfisoxazole decreased with time. Integrated pharmacokinetic models were applied to plasma and urine data to estimate the metabolic clearance of sulfisoxazole and the apparent volume of distribution of the N4‐acetylsulfisoxazole. Sulfisoxazole solution is absorbed readily by primarily a zero order process after a short lag period, indicative of rate‐determining gastric emptying. The classical Bratton‐Marshall assays were compared with an HPLC assay of both drug and metabolite. There was greater confidence in plasma levels of the metabolite from th
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