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Surgically affected sulfisoxazole pharmacokinetics in the morbidly obese
Author(s) -
Garrett Edward R.,
Suverkrup Richard S.,
Eberst Kathleen,
Yost Richard L.,
Patrick O'Leary J.
Publication year - 1981
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510020405
Subject(s) - sulfisoxazole , pharmacokinetics , metabolite , volume of distribution , chemistry , urine , distribution (mathematics) , pharmacology , high performance liquid chromatography , chromatography , medicine , antibiotics , biochemistry , mathematics , mathematical analysis , tetracycline
Abstract Intestinal 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 N 4 ‐ acetylsulfisoxazole metabolite. Dosing of this drug on a mgkg − 1 basis is contraindicated. Renal clearances of sulfisoxazole were reasonably constant within a study but those of the N 4 ‐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 N 4 ‐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.