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RS-61443--a new, potent immunosuppressive agent.
K P Platz1, H W Sollinger, D A Hullett
1Department of Surgery, University of Wisconsin School of Medicine, Madison 53792.
Transplantation
|January 1, 1991
Summary
RS-61443, a mycophenolic acid derivative, effectively prevented canine kidney transplant rejection when used in triple therapy with cyclosporine and methylprednisolone. Long-term use showed minimal toxicity, with gastrointestinal issues being dose-dependent.
Area of Science:
- Immunology
- Transplantation Medicine
- Pharmacology
Background:
- Renal allograft rejection remains a significant challenge in transplantation.
- Developing effective immunosuppressive agents is crucial for improving graft survival.
- RS-61443 is a novel semisynthetic derivative of mycophenolic acid with potential immunosuppressive properties.
Purpose of the Study:
- To evaluate the immunosuppressive activity and efficacy of RS-61443 in a canine renal allograft model.
- To determine the optimal combination therapy for preventing graft rejection.
- To assess the safety and toxicity profile of RS-61443 during long-term administration.
Main Methods:
- A canine renal allograft model was utilized with 33 subjects.
- RS-61443 was administered as monotherapy and in combination with cyclosporine (CsA) and methylprednisolone (MP).
- Graft survival times, adverse effects, and histological changes were monitored.
Main Results:
- Triple therapy (RS-61443 20 mg/kg, CsA 5 mg/kg, MP 0.1 mg/kg) significantly prolonged median graft survival to 122.4 days (p < 0.002).
- RS-61443 monotherapy (40 mg/kg) extended survival to 36.0 days (p < 0.05).
- Long-term RS-61443 administration showed no significant nephrotoxicity, hematotoxicity, or hepatotoxicity, apart from mild alkaline phosphatase elevation; gastrointestinal symptoms were dose-related.
Conclusions:
- Triple therapy including RS-61443 is highly effective in preventing canine renal allograft rejection.
- RS-61443 demonstrates a favorable long-term safety profile with manageable side effects.
- This study supports the potential of RS-61443 as a valuable immunosuppressant in organ transplantation.