RS-61443—A new, potent immunosuppressive agent

Academic Article

Abstract

  • The immunosuppressive activity of RS-61443, a sem-isynthetic derivative of mycophenolic acid, was examined in 33 canine renal allografts. Initial studies established that triple therapy consisting of 20 mg/kg RS- 61443 in combination with 5 mg/kg cyclosporine and 0.1 mg/kg methylprednisolone was the optimal combination to prevent graft rejection. The median survival time was 8.1 ±1.2 days in dogs without treatment (n=5), 8.5±1.7 days in the treatment control group (CsA 5 mg/ kg, MP 0.1 mg/kg; n=6), 36.0±9.6 days with RS-61443 monotherapy (40 mg/kg; n=6); and 122.4±38.75 days with triple therapy (n=16). Graft prolongation was statistically significant when compared with controls (P<0.05 and 0.002, respectively). Six recipients in the triple therapy group survived over 150 days without major adverse effects. Long-term administration of RS- 61443 (20 mg/kg/day) did not cause nephrotoxicity, hematotoxicity, or hepatotoxicity, with the exception of a slight elevation of the alkaline phosphatase levels. Gastrointestinal symptoms including gastritis, diarrhea, and anorexia were common, especially under 40 mg/kg RS-61443 monotherapy, and appeared to be dose-related. Despite its immunosuppressive activity, an increased susceptibility to bacterial or viral infections was not observed. Histological studies of the kidney grafts revealed slight interstitial cell infiltration without vas-cular or glomerular damage.© 1991 by Williams & Wilkins.
  • Author List

  • Platz KP; Sollinger HW; Hullett DA; Eckhoff DE; Eugui EM; Allison AC
  • Start Page

  • 27
  • End Page

  • 31
  • Volume

  • 51
  • Issue

  • 1