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.
D000328:Adult; D001682:Biological Availability; D001835:Body Weight; D005260:Female; D006801:Humans; D007082:Ileum / Q000601:surgery; D007583:Jejunum / Q000601:surgery; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D009765:Obesity / Q000378:metabolism* / Q000628:therapy; D013444:Sulfisoxazole / Q000031:analogs & derivatives / Q000378:metabolism*
C022966:N(4)-acetylsulfisoxazole; D013444:Sulfisoxazole