优化镰状细胞病患者的羟基脲治疗：药代动力学方法。
Optimizing Hydroxyurea Treatment for Sickle Cell Disease Patients: The Pharmacokinetic Approach.
作者信息
Nazon Charlotte, Sabo Amelia-Naomi, Becker Guillaume, Lessinger Jean-Marc, Kemmel Véronique, Paillard Catherine
机构信息
Hôpitaux Universitaires de Strasbourg, Centre de compétence pour les maladies constitutionnelles du globule rouge et de l'érythropoïèse, Service d'hématologie oncologie pédiatrique, Avenue Molière, 67200 Strasbourg, France.
Laboratoire de Pharmacologie et Toxicologie Neurocardiovasculaire, Faculté de Médecine, 11 rue Humann, 67085 Strasbourg, France.
出版信息
J Clin Med. 2019 Oct 16;8(10):1701. doi: 10.3390/jcm8101701.
BACKGROUND
Hydroxyurea (HU) is a FDA- and EMA-approved drug that earned an important place in the treatment of patients with severe sickle cell anemia (SCA) by showing its efficacy in many studies. This medication is still underused due to fears of physicians and families and must be optimized.
METHODS
We analyzed our population and identified HU pharmacokinetic (PK) parameters in order to adapt treatment in the future. Working with a pediatric population, we searched for the most indicative sampling time to reduce the number of samples needed.
RESULTS
Nine children treated by HU for severe SCA were included for this PK study. HU quantification was made using a validated gas chromatography/mass spectrometry (GC/MS) method. Biological parameters (of effectiveness and compliance) and clinical data were collected. None of the nine children reached the therapeutic target defined by Dong et al. as an area under the curve (AUC) = 115 h.mg/L; four patients were suspected to be non-compliant. Only two patients had an HbF over 20%. The 2 h sample was predictive of the medication exposure ( = 0.887).
CONCLUSIONS
It is urgent to be more efficient in the treatment of SCA, and pharmacokinetics can be an important asset in SCA patients.
背景
羟基脲（HU）是一种经美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）批准的药物，在多项研究中显示出其有效性，在重度镰状细胞贫血（SCA）患者的治疗中占据重要地位。由于医生和患者家属的担忧，这种药物的使用仍然不足，必须进行优化。
方法
我们分析了我们的研究人群，并确定了HU的药代动力学（PK）参数，以便在未来调整治疗方案。针对儿科人群，我们寻找最具指示性的采样时间，以减少所需的样本数量。
结果
9名接受HU治疗的重度SCA儿童被纳入这项PK研究。使用经过验证的气相色谱/质谱（GC/MS）方法对HU进行定量。收集了生物学参数（有效性和依从性）和临床数据。9名儿童中没有一人达到Dong等人定义的治疗目标，即曲线下面积（AUC）=115 h.mg/L；4名患者被怀疑不依从。只有2名患者的HbF超过20%。2小时的样本可预测药物暴露量（=0.887）。
结论
迫切需要提高SCA的治疗效率，药代动力学可能是SCA患者的一项重要资产。
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