Dos Santos Neres Joelma Santana, Yahouédéhou Sètondji Cocou Modeste Alexandre, Goncalves Marilda Souza
Laboratório de Investigação em Genética e Hematologia Translacional, Instituto Gonçalo Moniz, Fiocruz-BA, Salvador 40296-710, Brazil.
Laboratório de Pesquisas em Anemia, Faculdade de Farmácia, Universidade Federal da Bahia, Salvador 40170-110, Brazil.
Pharmaceuticals (Basel). 2023 Jun 8;16(6):857. doi: 10.3390/ph16060857.
Inconsistent therapeutic responses have been observed among patients with sickle cell anemia (SCA) undergoing hydroxyurea (HU) following the adoption of the standardized protocol. Moreover, this treatment regimen necessitates a prolonged period to reach the maximum tolerated dose in which beneficial therapeutic effects are observed in most SCA patients. To overcome this limitation, several studies have performed HU dose adjustments in SCA patients based on individualized pharmacokinetic profiles. The present systematic mini-review aims to select and analyze published data to present an overview of HU pharmacokinetics studies performed in SCA patients, as well as evaluate the effectiveness of the dose adjustment strategy. A systematic search was performed in the Embase, Pubmed, Scopus, Web of Science, Scielo, Google Scholar, and the Virtual Library of Health databases from December 2020 to August 2022, with a total of five studies included. Inclusion criteria consisted of studies in which the dose adjustment was performed in SCA patients based on pharmacokinetic parameters. Quality analyzes were performed using QAT, while data synthesis was performed according to the Cochrane Manual of Systematic Reviews of Interventions. Analysis of the selected studies revealed improved HU treatment effectiveness using personalized dosages in SCA patients. Moreover, several laboratory parameters were utilized as biomarkers of the HU response, and methods designed to simplify the adoption of this practice were presented. Despite the scarcity of studies on this topic, HU-personalized treatment based on individualized pharmacokinetic profiles represents a viable alternative for SCA patients who are candidates for HU therapy, especially for pediatric patients. Registration number: PROSPERO CRD42022344512.
在采用标准化方案后，接受羟基脲（HU）治疗的镰状细胞贫血（SCA）患者中观察到了不一致的治疗反应。此外，这种治疗方案需要较长时间才能达到最大耐受剂量，而大多数SCA患者在此剂量下可观察到有益的治疗效果。为克服这一局限性，多项研究根据个体药代动力学特征对SCA患者进行了HU剂量调整。本系统性小型综述旨在筛选和分析已发表的数据，以概述在SCA患者中进行的HU药代动力学研究，并评估剂量调整策略的有效性。我们于2020年12月至2022年8月在Embase、Pubmed、Scopus、Web of Science、Scielo、Google Scholar和虚拟健康图书馆数据库中进行了系统检索，共纳入五项研究。纳入标准包括基于药代动力学参数对SCA患者进行剂量调整的研究。使用QAT进行质量分析，同时根据《Cochrane系统评价干预措施手册》进行数据合成。对所选研究的分析表明，在SCA患者中使用个性化剂量可提高HU治疗效果。此外，还利用了多个实验室参数作为HU反应的生物标志物，并提出了旨在简化这种做法应用的方法。尽管关于该主题的研究较少，但基于个体药代动力学特征的HU个性化治疗对于适合HU治疗的SCA患者，尤其是儿科患者而言，是一种可行的选择。注册号：PROSPERO CRD42022344512。
