Influence of obesity on sulfonamide disposition in Zucker rats

Abstract

The genetically obese Zucker rat was used as a model of obesity and compared to its lean littermate to assess and quantify obesity-altered changes in the in vivo disposition of six sulfonamides. Body composition determination indicated that the obese rats were twice the weight of lean rats and a distinct trend towards an increase in fat free mass and total body water was observed. The sulfonamide blood concentration was measured by colorimetry after a 7 mg/kg intravenous dose. All sulfonamides exhibited a biexponential decline of blood concentration with time. The volume of distribution and clearance of sulfanilamide in lean and obese rats were similar resulting in similar elimination half-lives. A decrease in clearance coupled with a trend towards an increase in volume of distribution prolonged the elimination half-life of sulfadiazine in obese rats. For sulfapyridine, sulfamerazine, sulfisomidine and sulfisoxazole, increases in the volumes of distribution and clearances resulted in similar elimination half-lives in lean and obese rats. The free fractions of the sulfonamides were significantly increased in the serum of obese rats, the influence of which on the volume of distribution and clearance is discussed.