Hsu Daphne T
Columbia University Medical Center, Morgan Stanley Children's Hospital of New York Presbyterian, NY 10032, USA.
Pediatr Transplant. 2005 Jun;9(3):416-21. doi: 10.1111/j.1399-3046.2005.00352.x.
Solid organ transplantation has become accepted therapy for the treatment of end-stage organ dysfunction in children. As early management of the pediatric transplant recipient has improved, important age-related differences in long-term patient outcomes have become apparent. Late morbidity and mortality can, in most cases, be attributed to the consequences of long-term immunosuppression: graft loss from under-immunosuppression or an increased incidence of cancer, hypertension, renal failure or diabetes from over-immunosuppression. Age-related differences in both biological and psychological factors play an important role in the optimization of therapy in the transplanted child. Important age-related differences have been demonstrated in all phases of pharmacokinetics: absorption, distribution, metabolism and elimination. Information regarding specific age-related pharmacokinetic differences is lacking for many immunosuppressive medications. Further study using physiologically based pharmacokinetic (PBPK) models will lead to more specific recommendations for age-based immunosuppression protocols. Non-adherence is common among solid organ transplant recipients of all ages and the consequences of non-adherence include increased rejection, late graft loss and death. The biological and psychological developmental changes that occur during adolescence place the transplanted adolescent at an even higher risk of non-adherence and poor outcome than other age groups. Further studies to elucidate the importance of both age-related pharmacokinetic and behavioral factors are needed to formulate therapeutic interventions that would improve adherence and patient outcomes.
实体器官移植已成为治疗儿童终末期器官功能障碍的公认疗法。随着小儿移植受者早期管理的改善，长期患者预后方面重要的年龄相关差异已变得明显。在大多数情况下，晚期发病率和死亡率可归因于长期免疫抑制的后果：免疫抑制不足导致移植物丢失，或免疫抑制过度导致癌症、高血压、肾衰竭或糖尿病发病率增加。生物学和心理因素方面的年龄相关差异在优化移植儿童的治疗中起着重要作用。在药代动力学的所有阶段：吸收、分布、代谢和消除，都已证明存在重要的年龄相关差异。许多免疫抑制药物缺乏关于特定年龄相关药代动力学差异的信息。使用基于生理学的药代动力学（PBPK）模型进行进一步研究将为基于年龄的免疫抑制方案带来更具体的建议。不依从在所有年龄段的实体器官移植受者中都很常见，不依从的后果包括排斥反应增加、晚期移植物丢失和死亡。青春期发生的生物学和心理发育变化使移植青少年比其他年龄组面临更高的不依从风险和不良预后。需要进一步研究以阐明年龄相关药代动力学和行为因素的重要性，从而制定能够改善依从性和患者预后的治疗干预措施。
