Surgically affected sulfisoxazole pharmacokinetics in the morbidly obese

Intestinal bypass surgery in 4 morbidly obese female (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 mg kg-1 basis 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 the HPLC method.