Sulfamethazine absorption and disposition: effect of surgical procedures for gastroduodenal ulcers

This study was designed to determine whether the surgical procedures for gastroduodenal ulcers influence sulfamethazine (SMZ) absorption and disposition. Prior to and on the average 79 days after surgery, eight patients received 10 mg kg-1 of sulfamethazine orally. Blood samples were obtained at regular intervals over 24 h and urine was collected for 48 h. Vagotomy with pyloroplasty or with gastrojejunostomy had no effect on SMZ kinetics. Vagotomy with partial gastrectomy decreased the SMZ plasma peak concentrations from 43.9 +/- 7.1 (mean +/- SEM) to 17.2 +/- 5.2 micrograms ml-1 (p less than 0.05) and increased the time required to reach this peak from 2.6 +/- 0.8 to 9.8 +/- 2.8 h (p less than 0.05). SMZ rate constant of absorption decreased only slightly (1.22 +/- 0.45 to 0.24 +/- 0.07 h-1) and SMZ bioavailability was not affected at all. In two (out of four) patients, SMZ volume of distribution and total body clearance increased, as reflected in the 41 per cent decrease in the mean area under the SMZ plasma concentration-time curve. No changes were detected in SMZ protein binding. Computer simulations indicated that in some subjects SMZ plasma concentrations at steady state could be 76 per cent lower following vagotomy with partial gastrectomy than before surgery. It was concluded that vagotomy and antrectomy with a gastroduodenostomy or Billroth I reconstruction decreased the rate of SMZ absorption and only in some subjects increased the SMZ volume of distribution and rate of elimination. The possible mechanisms involved in these reported kinetic changes are discussed.