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

Abstract

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.

The Influence of Bypass Procedures and Other Anatomical Changes in the Gastrointestinal Tract on the Oral Bioavailability of Drugs

“…Similarly, the absorption of sulfamethazine (also an acidic sulfonamide) was delayed (but not reduced) in patients with gastrectomy combined with vagotomy (n ¼ 4). 12 The absorption in patients with only vagotomy (n ¼ 4) however was not impaired. 12 Taking these studies into account, changes in absorption are more likely attributed to the association of vagotomy with partial gastrectomy.…”

“…The absorption phase of sulfafurazole therefore seems to be prolonged in patients with gastrectomy combined with vagotomy. Similarly, the absorption of sulfamethazine (also an acidic sulfonamide) was delayed (but not reduced) in patients with gastrectomy combined with vagotomy (n = 4) . The absorption in patients with only vagotomy (n = 4) however was not impaired .…”

“…In fact, AUC values observed after oral administration in patients with a duodenostomy or a jejunostomy (ranging from 15 to 60 cm distal from the duodenojejunal flexure; n ¼ 5) were significantly lower compared to those observed in healthy volunteers with a normal GI tract (n ¼ 32). 17 In addition, pylorus preserving pancreatoduodenectomy (PPPD; n ¼ 12) and jejunoileal bypass (JIB; n ¼ 3; both preserving the duodenojenunal 12,13 Delayed gastric emptying 12,13 Vagotomy with pyloroplasty Denervation of the gastric musculature Increased gastric pH 12,13 Widening the muscular opening of the pyloric sphincter…”

Drug Absorption in Gastrointestinal Disease and Surgery

“…The effect of common surgical procedures of the upper GI tract on the absorption of an acidic sulphonamide, sulfamethazine, was assessed in 8 439 patients (Calvo et al 1987). The procedures either involved no loss of GI surface (a vagotomy with a pyloroplasty or a gastrojejunostomy) or a loss of approximately 30% of gastric surface area (ABI with vagotomy); each group was equally represented.…”

“…There is conflicting evidence as to which factor is more important. In the study of sulfamethazine absorption, all patients had a vagotomy, yet malabsorption was seen only in those with ABI and vagotomy (Calvo et al 1987), implying that alterations in pH contribute more to malabsorption following these procedures. Vagotomy is known to increase gastric emptying time (Buckler 1967).…”