Martial Lisa C, Jacobs Bart A W, Cornelissen Elisabeth A M, de Haan Anton F J, Koch Birgit C P, Burger David M, Aarnoutse Rob E, Schreuder Michiel F, Brüggemann Roger J M
Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands.
Radboud Institute for Health Sciences, Radboud University, Nijmegen, The Netherlands.
Pediatr Transplant. 2016 Jun;20(4):492-9. doi: 10.1111/petr.12695. Epub 2016 Feb 29.
MPA is an immunosuppressive agent used to prevent graft rejection after renal transplantation. MPA shows considerable inter- and intraindividual variability in exposure in children and has a defined therapeutic window, and TDM is applied to individualize therapy. We aimed to study the exposure to MPA measured as the AUC in pediatric renal transplant patients, to identify factors influencing exposure and to assess target attainment. Children transplanted between 1998 and 2014 in a single center were included. Two groups were identified: Group 1 (AUC <3 wk post-transplantation) and Group 2 (AUC >18 months post-transplantation). Therapeutic targets were set at: AUC0-12h of 30-60 mg h/L. A total of 39 children were included in Group 1 (median age 13.3 yr) vs. 14 in Group 2 (median age 13.4 yr). AUC0-12h was 29.7 mg h/L in Group 1 and 56.6 mg h/L in Group 2, despite a lower dosage in Group 2 (584 and 426 mg/m(2) , respectively). About 46% of patients reached the target AUC0-12h in Group 1. Time since transplantation and serum creatinine were significantly associated with MPA exposure (p < 0.001), explaining 36% of the variability. Individualization of the mycophenolate dose by more intense and more early TDM could improve target attainment.
霉酚酸酯(MPA)是一种免疫抑制剂,用于预防肾移植后的移植物排斥反应。MPA在儿童中的暴露量存在显著的个体间和个体内差异,且有明确的治疗窗,因此采用治疗药物监测(TDM)来实现个体化治疗。我们旨在研究以曲线下面积(AUC)衡量的儿科肾移植患者中MPA的暴露情况,确定影响暴露的因素,并评估目标达成情况。纳入了1998年至2014年在单一中心接受移植的儿童。确定了两组:第1组(移植后<3周的AUC)和第2组(移植后>18个月的AUC)。治疗目标设定为:AUC0-12h为30-60mg·h/L。第1组共纳入39名儿童(中位年龄13.3岁),第2组纳入14名儿童(中位年龄13.4岁)。第1组的AUC0-12h为29.7mg·h/L,第2组为56.6mg·h/L,尽管第2组的剂量较低(分别为584和426mg/m²)。第1组中约46%的患者达到了目标AUC0-12h。移植后的时间和血清肌酐与MPA暴露显著相关(p<0.001),解释了36%的变异性。通过更强化和更早期的TDM对霉酚酸剂量进行个体化调整可提高目标达成率。