| The female, 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 sulfanilamide, sulfadiazine, sulfapyridine, sulfamerazine, sulfisomidine, and sulfisoxazole. Body composition of the obese rats was determined after the estimation of total body water by tritium dilution. The obese rats were at least twice the weight of lean rats and exhibited a distinct trend towards an increase in fat, fat free mass and total body water.;Since V(,ss) or V(,z) of the sulfonamides did not exceed total body water of the animals, their administration on the basis of mg/kg actual body weight is contraindicated.;The sulfonamide blood concentration was measured by colorimetry after a 7 mg/kg actual body weight intravenous dose. All sulfonamides exhibited a biexponential decline of blood concentration with time. There was no difference in V(,ss) or V(,z) and CL of sulfanilamide in lean and obese rats. As a result, t(, 1/2) and MRT remained unchanged. A decrease in the CL of sulfadiazine in obese rats coupled with a trend towards an increase in V(,ss) or V(,z) resulted in a prolonged t(, 1/2) and MRT of sulfadiazine in obese rats. For sulfapyridine, sulfamerazine, sulfisomidine, and sulfisoxazole, an increase in V(,ss) or V(,z) and CL was observed in obese rats resulting in a similar t(, 1/2) and MRT for lean and obese rats. The free fraction of the sulfonamides was significantly increased in the serum from obese rats which did not result in a proportional increase in CL because the CL(,int) of the sulfonamides was reduced. The CL(,int) of sulfanilamide and sulfapyridine remained unchanged. The elevated free fraction was attributed to conformational changes of the albumin molecule or the presence of binding inhibitors in the serum of obese rats. |
PDF Full Text Request