Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA.
Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA.
Expert Opin Drug Metab Toxicol. 2021 Jul;17(7):747-765. doi: 10.1080/17425255.2021.1943356. Epub 2021 Jun 29.
Graft survival in pediatric kidney transplant patients has increased significantly within the last three decades, correlating with the discovery and utilization of new immunosuppressants as well as improvements in patient care. Despite these developments in graft survival for patients, there is still improvement needed, particularly in long-term care in pediatric patients receiving grafts from deceased donor patients. Maintenance immunosuppressive therapies have narrow therapeutic indices and are associated with high inter-individual and intra-individual variability. In this review, we examine the impact of pharmacokinetic variability on renal transplantation and its association with age, genetic polymorphisms, drug-drug interactions, drug-disease interactions, renal insufficiency, route of administration, and branded versus generic drug formulation. Pharmacodynamics are outlined in terms of the mechanism of action for each immunosuppressant, potential adverse effects, and the utility of pharmacodynamic biomarkers. Acquiring abetter quantitative understanding of immunosuppressant pharmacokinetics and pharmacodynamic components should help clinicians implement treatment regimens to maintain the balance between therapeutic efficacy and drug-related toxicity.
在过去的三十年中,儿科肾移植患者的移植物存活率显著提高,这与新免疫抑制剂的发现和使用以及患者护理的改善有关。尽管患者的移植物存活率有所提高,但仍需进一步改善,特别是在接受已故供体患者移植物的儿科患者的长期护理方面。维持性免疫抑制治疗具有狭窄的治疗指数,并且与个体间和个体内的变异性高相关。在这篇综述中,我们研究了药代动力学变异性对肾移植的影响及其与年龄、遗传多态性、药物相互作用、药物-疾病相互作用、肾功能不全、给药途径以及品牌与仿制药制剂的关系。药效学根据每种免疫抑制剂的作用机制、潜在的不良反应以及药效学生物标志物的实用性进行了描述。更好地定量了解免疫抑制剂的药代动力学和药效学成分,应有助于临床医生实施治疗方案,以维持治疗效果与药物相关毒性之间的平衡。