Regazzi M B, Alessiani M, Rinaldi M
Department of Pharmacology, IRCCS Policlinico S. Matteo, Pavia, Italy.
Transplant Proc. 2005 Jul-Aug;37(6):2675-8. doi: 10.1016/j.transproceed.2005.06.104.
New immunosuppressive strategies that can prevent both acute and chronic rejection are being investigated to achieve graft tolerance and to minimize side effects and toxicity that may lead to graft loss. Drug pharmacokinetics and pharmacodynamics, as well as pharmacogenetics, all play a role in customizing treatment to the individual patient. To improve patient compliance, new drug formulations are on trial, such as the modified- release oral form of tacrolimus MR4 for once daily administration, which seems to be equivalent to bid administration in terms of steady-state exposure. Monoclonal/polyclonal antibodies are increasingly used in the induction phase in protocols where steroids are discontinued early. However, discontinuing steroids carries a high risk of acute rejection or organ failure in some subgroups of patients. The supposed benefit of steroid discontinuation may not be enjoyed by all patients. Minimizing anticalcineurin agents may prove to be similarly or even more advantageous. The use of new drugs and new combinations has greatly improved short-term transplant outcomes. The new goal is, therefore, to improve long-term results and particularly to prevent chronic rejection, thus increasing patient and organ survival.
目前正在研究能够预防急性和慢性排斥反应的新型免疫抑制策略,以实现移植物耐受,并将可能导致移植物丢失的副作用和毒性降至最低。药物的药代动力学、药效学以及药物遗传学,在为个体患者定制治疗方案方面均发挥着作用。为提高患者的依从性,新型药物制剂正在进行试验,例如他克莫司缓释口服制剂MR4,每日服用一次,就稳态血药浓度而言,其似乎等同于每日两次给药。在早期停用类固醇的方案中,单克隆/多克隆抗体在诱导期的使用越来越多。然而,在某些患者亚组中,停用类固醇会带来急性排斥反应或器官衰竭的高风险。并非所有患者都能享受到停用类固醇带来的预期益处。减少钙调神经磷酸酶抑制剂的使用可能同样或更具优势。新药和新联合用药方案的使用极大地改善了短期移植效果。因此,新的目标是改善长期效果,尤其是预防慢性排斥反应,从而提高患者生存率和器官存活率。