Prolongation of intraperitoneal segmental pancreatic allografts in primates receiving cyclosporin A

In this study the efficacy of the new immunosuppressive agent, cyclosporin A (CYA), was examined in a model of segmental, intraperitoneal pancreatic allotransplantation with free duct drainage in totally pancreatectomized, outbred Chacma baboons. CYA, in doses of 25 to 50 mg/kg/day administered to recipients of heterotopic segmental (tail) allografts, produced a slight but significant prolongation of graft survival. CYA (25 to 85 mg/kg/day), administered orally after pancreatic transplantation gave daily serum trough levels of CYA that ranged from 300 to 600 ng/ml. Mean serum trough levels on the first postoperative day in recipients of 50 mg/kg/day were 121.1 +/- 61.6 ng/ml. There was a wide variation in daily serum trough levels exhibited between primates on the same daily oral dose, and there was no correlation between absolute serum trough levels of CYA and rejection. It is postulated that adequate serum CYA levels were not achieved by the oral administration of the drug to ensure allograft survival beyond 60 days in pancreatectomized recipients. Adverse effects occurred frequently and included anorexia, diarrhea, and tremors and were in direct proportion to the quantity of CYA required to prolong graft survival. Free duct drainage into the abdominal cavity frequently resulted in pancreatic ascites, which necessitated paracentesis, indicating that this method of duct drainage has limited clinical application. Although heterotopic autotransplantation or allotransplantation of the tail of the pancreas in the baboon was capable of maintaining normoglycemia in pancreatectomized baboons, glucose intolerance, reduced K values, and hypoinsulinemia were consistent findings during glucose tolerance tests, suggesting that an insufficient islet cell mass had been transplanted.