Levy G A
Multi Organ Transplant Program, Toronto Hospital, University of Toronto, Ontario, Canada.
Transplant Proc. 1996 Aug;28(4):2225-8.
In conclusion, Neoral gives more consistent drug absorption, achieving better pharmacokinetic predictability. Among other advantages, this results in a close correlation between trough blood levels and drug exposure (AUC) so that trough blood levels can be used as a more meaningful monitoring parameter when using the new formulation. Studies have also now confirmed that absorption of Neoral is bile independent, making it more useful in the early postoperative period and in the setting of cholestasis and rejection. Furthermore, studies have now demonstrated that in patients who have problems absorbing Sandimmune such as patients with cystic fibrosis, pancreatitis or Crohn's disease, conversion to Neoral results in correction of malabsorption of CyA. More recent data suggests that induction with Neoral results in a marked reduction in the incidence of acute rejection and allows for withdrawal of steroids and normalization of blood glucose, serum triglyceride, and cholesterol even when withdrawal is done 1 year after transplantation. Despite the high Cmax and AUC, there appears to be no increased toxicity in patients treated with Neoral. Issues that need to be addressed in the future include long-term toxicity associated with maintaining high Cmax and AUC and confirmation that the use of Neoral results in a reduction of both acute and chronic rejection.
总之,新山地明的药物吸收更具一致性,实现了更好的药代动力学可预测性。除其他优点外,这使得谷浓度血药水平与药物暴露量(AUC)之间存在密切相关性,因此在使用新剂型时,谷浓度血药水平可作为更有意义的监测参数。研究现在也证实,新山地明的吸收不依赖胆汁,这使其在术后早期以及胆汁淤积和排斥反应的情况下更有用。此外,研究现已表明,对于吸收环孢素(Sandimmune)有问题的患者,如囊性纤维化、胰腺炎或克罗恩病患者,改用新山地明可纠正环孢素A(CyA)的吸收不良。最新数据表明,使用新山地明进行诱导可显著降低急性排斥反应的发生率,甚至在移植1年后停药时,也可停用类固醇并使血糖、血清甘油三酯和胆固醇恢复正常。尽管新山地明的Cmax和AUC较高,但接受其治疗的患者似乎并未出现毒性增加的情况。未来需要解决的问题包括与维持高Cmax和AUC相关的长期毒性,以及确认使用新山地明可降低急性和慢性排斥反应的发生率。