Marini Valeria, Pinto Valeria Maria, Stella Manuela, Fucile Carmen, Lantieri Francesca, Luci Giacomo, Gianesin Barbara, Bacigalupo Lorenzo, Forni Gian Luca, Mattioli Francesca
Clinical Pharmacology Unit, EO Ospedali Galliera, Mura delle Cappuccine, n. 14. I-16128 Genoa, Italy.
Department of Internal Medicine, Clinical Pharmacology and Toxicology Unit, University of Genoa, Viale Benedetto XV, n. 2. I-16132 Genoa, Italy.
Curr Drug Metab. 2022;23(13):1072-1079. doi: 10.2174/1389200224666221209144420.
Iron-chelation therapy is life-saving in patients on a chronic transfusion regimen as it reduces organ damage related to iron deposition in the tissues. Deferasirox, an iron-chelator, is characterized by pharmacokinetics variability, and some patients may discontinue the treatment due to toxicities.
Understanding whether deferasirox plasma levels are related to patients' specific characteristics could help to optimize DFX dosage.
We analyzed deferasirox plasma concentration in 57 transfusion-dependent anemic patients using the HPLC method in this prospective-retrospective cohort study. All outpatients (3 to 98 years) were treated with deferasirox (film-coated tablet) for at least one year (median dose, 16.5 mg/Kg once a day). Deferasirox plasma concentration was normalized for dose/Kg (C/dose) and corrected with a linear regression model that relates C/dose and the time of blood sampling (C/dose).
No significant differences in C/dose were found between males and females, either between different types of hemoglobinopathies or depending on the presence of the UGT1A1*28 polymorphism. C/dose has a positive and significant correlation with age, creatinine, and direct bilirubin. C/dose, instead, has a negative and significant correlation with Liver Iron Concentration (LIC), ferritin, and eGFR. C/dose was significantly different between three age categories <18yrs, 18-50yrs, and >50yrs, with C/dose median values of 1.0, 1.2, and 1.5, respectively.
The study evidenced that to ensure the efficacy of deferasirox in terms of control over LIC and, at the same time, a lesser influence on renal function, the dose of the drug to be administered to an elderly patient could be reduced.
铁螯合疗法对接受慢性输血治疗的患者来说是挽救生命的，因为它能减少与组织中铁沉积相关的器官损伤。铁螯合剂地拉罗司具有药代动力学变异性，一些患者可能因毒性而停止治疗。
了解地拉罗司血浆水平是否与患者的特定特征相关，有助于优化地拉罗司的剂量。
在这项前瞻性-回顾性队列研究中，我们使用高效液相色谱法分析了57例依赖输血的贫血患者的地拉罗司血浆浓度。所有门诊患者（3至98岁）接受地拉罗司（薄膜包衣片）治疗至少一年（中位剂量，16.5mg/Kg，每日一次）。地拉罗司血浆浓度按剂量/Kg进行标准化（C/剂量），并用线性回归模型进行校正，该模型将C/剂量与采血时间相关联（C/剂量）。
在男性和女性之间，不同类型的血红蛋白病之间，或根据UGT1A1*28多态性的存在情况，C/剂量均未发现显著差异。C/剂量与年龄、肌酐和直接胆红素呈正相关且具有统计学意义。相反，C/剂量与肝脏铁浓度（LIC）、铁蛋白和估算肾小球滤过率（eGFR）呈负相关且具有统计学意义。在<18岁、18 - 50岁和>50岁这三个年龄组之间，C/剂量存在显著差异，C/剂量的中位数分别为1.0、1.2和1.5。
该研究证明，为确保地拉罗司在控制LIC方面的疗效，同时减少对肾功能的影响，可以降低老年患者的给药剂量。
