Optimizing Hydroxyurea Treatment for Sickle Cell Disease Patients: The Pharmacokinetic Approach

Journal of Clinical Medicine

Catherine Paillard¹  Charlotte Nazon¹  Guillaume Becker²  Jean-Marc Lessinger³  Amelia-Naomi Sabo³  Véronique Kemmel³ 

[1] 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;Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, Laboratoire de Biochimie et Biologie Moléculaire, Avenue Molière, 67200 Strasbourg, France;Laboratoire de Pharmacologie et Toxicologie Neurocardiovasculaire, Faculté de Médecine, 11 rue Humann, 67085 Strasbourg, France;

关键词: sickle cell disease;    sickle cell anemia;    hydroxyurea;    pharmacokinetics;   

DOI  :  10.3390/jcm8101701

来源: DOAJ

【 摘 要 】

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 (r² = 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.

【 授权许可】

Unknown