McCauley J
University of Pittsburgh School of Medicine, Transplantation Institute, PA 15213.
Curr Opin Nephrol Hypertens. 1993 Jul;2(4):662-9. doi: 10.1097/00041552-199307000-00017.
FK506, a new macrolide immunosuppressant agent, is approximately 100 times more potent than cyclosporine. Early clinical trials demonstrated FK506 to be effective in reversing refractory rejection in liver, kidney, and heart transplantation. Like cyclosporine, FK506 has significant nephrotoxicity. The clinical presentation and morphology of FK506 nephrotoxicity are identical to those of cyclosporine. Many animal and in vitro studies suggest that FK506 may be less nephrotoxic than cyclosporine. Studies in humans after transplantation have not confirmed this advantage. FK506 has pursued the same pattern in drug development as cyclosporine, with progressive dose reductions over the years. Studies from this early developmental period suggest that the nephrotoxicity of FK506 and cyclosporine in clinical use are approximately equivalent. Further refinement in the clinical use of FK506 will likely reduce its toxicity further. Appropriate studies conducted at that stage will determine which drug possesses less nephrotoxicity.
FK506是一种新型大环内酯类免疫抑制剂，其效力比环孢素强约100倍。早期临床试验表明，FK506在逆转肝、肾和心脏移植中的难治性排斥反应方面有效。与环孢素一样，FK506具有显著的肾毒性。FK506肾毒性的临床表现和形态与环孢素相同。许多动物和体外研究表明，FK506的肾毒性可能比环孢素小。移植后人体研究尚未证实这一优势。FK506在药物研发过程中遵循了与环孢素相同的模式，多年来剂量逐渐降低。这个早期研发阶段的研究表明，临床使用中FK506和环孢素的肾毒性大致相当。FK506临床应用的进一步优化可能会进一步降低其毒性。在那个阶段进行的适当研究将确定哪种药物的肾毒性较小。
