Maturation of dose-corrected tacrolimus predose trough levels in pediatric kidney allograft recipients
Maturation of dose-corrected tacrolimus predose trough levels in pediatric kidney allograft recipients
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DOI：
10.1097/tp.0b013e31816b431a
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发表时间：
2008-04-27
期刊：
影响因子：
6.2
通讯作者：
Sarwal, Minnie
中科院分区：
文献类型：
--
作者：
Naesens, Maarten;Salvatierra, Oscar;Sarwal, Minnie
背景与成人肾移植受者相比，他克莫司药代动力学的长期演变和临床决定因素得到了很好的研究，但对他克莫司在儿童肾移植受者中的药代动力学的长期演变知之甚少。105例儿童肾移植受者，均接受无皮质类固醇免疫抑制方案治疗。在移植后3、6、9、12、18和24个月记录他克莫司剂量和给药前谷值（C-0）水平的变化，以及在移植后前2年获得的所有C-0水平。分析他克莫司暴露参数的演变和临床决定因素。在儿童受者肾移植后的前2年，剂量校正的他克莫司C-0水平（C-0/剂量/kg）增加（P= 0.00 1）。随着时间的推移，这种剂量需求的降低仅在移植时5岁以上的儿童中显著（< 5岁、5-12岁和> 12岁的年龄组分别为P= 0.38、0.03和0.00 1）。此外，与老年受者相比，年轻受者的剂量需求（剂量/kg）显著更高（P=0.0002）。儿童肾移植受者在移植后随着时间的推移，剂量校正的他克莫司给药前谷浓度逐渐成熟。这不能用皮质类固醇使用的差异来解释，因为所有患者都接受了无皮质类固醇方案治疗。年轻受者的较高剂量要求和最年轻受者中他克莫司成熟的缺乏表明他克莫司肠道首过效应、代谢或分布的年龄依赖性变化起作用。年龄特异性他克莫司给药算法是否会改善结果需要进一步研究。
Background. In contrast to adult kidney recipients, in whom the long-term evolution and clinical determinants of tacrolimus pharmacokinetics are well studied, less is known about the long-term evolution of tacrolimus pharmacokinetics in pediatric kidney transplant recipients.Methods. One-hundred and five pediatric recipients of a kidney allograft, all treated with a corticosteroid-free immunosuppressive protocol, were included. The evolution of tacrolimus doses and predose trough (C-0) levels was recorded at 3, 6, 9, 12, 18, and 24 months after transplantation, as well as all C-0 levels obtained in the first 2 years after transplantation. The evolution and clinical determinants of tacrolimus exposure parameters were analyzed.Results. Dose-corrected tacrolimus C-0 levels (C-0/dose/kg) increased in the first 2 years after kidney transplantation in pediatric recipients (P= 0.00 1). This decrease in dose requirement by time was only significant in children older than 5 years at the time of transplantation (P= 0.38, 0.03, and 0.00 1 for age groups < 5, 5-12, and > 12 years, respectively). In addition, the younger patients had significantly higher dose requirements (dose/kg) compared with older recipients (P=0.0002).Conclusion. Pediatric kidney transplant recipients exhibit maturation of dose-corrected tacrolimus predose trough levels with time after transplantation. This cannot be explained by differences in corticosteroid use, because all patients were treated with a corticosteroid-free protocol. The higher dose requirements for younger recipients and the absence of tacrolimus maturation in the youngest recipients suggest that age-dependent changes in tacrolimus intestinal first-pass effect, metabolism, or distribution play a role. Whether age-specific tacrolimus dosing algorithms will improve outcome needs further study.