Department of Pediatric Nephrology, King Hussien Medical Center, Amman, Jordan.
Department of Applied Pharmaceutical Sciences, School of Pharmacy, Isra University, Amman, Jordan.
Br J Clin Pharmacol. 2019 Jul;85(7):1434-1442. doi: 10.1111/bcp.13911. Epub 2019 May 11.
The aim of this study was, to use a multiple methods approach, including, for the first time, dried blood spot (DBS) sampling with population pharmacokinetic interpretation, to assess adherence to mycophenolate in children with kidney transplant. A second aim was to identify patient/parental factors that influenced adherence and to link adherence behaviour to clinical outcomes.
A convenience sample of 33 children with kidney transplant (age ≤ 18 years) who had been prescribed mycophenolate for at least 3 months were recruited from participating outpatient clinics in the UK and Jordan. Medication adherence was determined via self-report questionnaires, medication refill data from dispensing records, and via mycophenolic acid concentrations in plasma and DBS samples obtained from children during a clinic visit.
Through triangulation of results from the different methodological approaches a total of 12 children (36.4%) were deemed to be nonadherent with their prescribed mycophenolate treatment. Logistic regression analysis indicated that nonadherence was significantly associated with the presence of mycophenolate side effects. Poor adherence was positively linked to measures of poor clinical outcomes (hospitalisation and the need for kidney biopsy).
Despite the imperative regarding medication adherence to help prevent organ rejection, a significant proportion of children are not fully adherent with their therapy. Side-effects appear to be an important factor leading to nonadherence. Measurement of mycophenolate in DBS samples, coupled with the use of population pharmacokinetics modelling, was a convenient direct approach to assessing adherence in children with kidney transplant and has the potential to be introduced into routine practice.
本研究旨在采用多种方法，包括首次采用干血斑（DBS）采样并进行群体药代动力学解释，评估儿童肾移植患者对吗替麦考酚酯的依从性。第二个目的是确定影响依从性的患者/家长因素，并将依从性行为与临床结果联系起来。
从英国和约旦参与的门诊诊所中招募了 33 名接受至少 3 个月吗替麦考酚酯治疗的肾移植儿童（年龄≤18 岁）作为便利样本。通过自我报告问卷、配药记录中的药物补充数据以及在就诊期间从儿童获得的血浆和 DBS 样本中的吗替麦考酚酸浓度来确定药物依从性。
通过不同方法学方法的结果的三角测量，共有 12 名儿童（36.4%）被认为不遵守他们规定的吗替麦考酚酯治疗方案。逻辑回归分析表明，不依从与吗替麦考酚酯的副作用存在显著相关性。不良依从性与不良临床结果（住院和需要肾活检）的测量呈正相关。
尽管需要严格遵守药物治疗以预防器官排斥，但相当一部分儿童并未完全遵守其治疗方案。副作用似乎是导致不依从的一个重要因素。DBS 样本中吗替麦考酚酯的测量，结合群体药代动力学模型的使用，是一种方便的直接评估肾移植儿童依从性的方法，有可能引入常规实践。
