Comparison of Two Types of Amino Acid Solutions on 177Lu-Dotatate Pharmacokinetics and Pharmacodynamics in Patients with Metastatic Gastroenteropancreatic Neuroendocrine Tumors
Comparison of Two Types of Amino Acid Solutions on 177Lu-Dotatate Pharmacokinetics and Pharmacodynamics in Patients with Metastatic Gastroenteropancreatic Neuroendocrine Tumors
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DOI：
10.2174/1874471015666211228123525
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发表时间：
2022-01-01
影响因子：
2.3
通讯作者：
Chatelut, Etienne
中科院分区：
文献类型：
--
作者：
Lambert, Marie;Dierickx, Lawrence;Chatelut, Etienne
背景：LU-177-二酸用于治疗生长抑素受体阳性的无法手术的进行性胃肠道神经内分泌肿瘤。对氨基酸（AAS）的共融合以防止肾脏毒性。目标：本研究旨在量化两种类型的AA鸡尾酒对LU-177-DOTATATE的药代动力学和毒性的影响：四种注射：四次注射7400的注射每位患者给予MBQ LU-177--二酸，施用Primene（R）为10％（含有20 AAS的鸡尾酒为22G赖氨酸和16.8 g精氨酸）或Lysakare（R）（含25 g赖氨酸和25 g）精氨酸G）。在每个周期收集9个血液样本。使用NONMEM（版本7.4.1）根据基于人群的模型分析放射性时间数据。每个周期后都评估了肾脏和血液学毒性。结果：1,678 LU-177-二他血浆浓度与时间与时间相对于时间的时间分析了83例PRIMENE（R）（n = 45 pts）或Lysakare（n = 45 pts）或Lysakare（r）（r）（r）（n = 36 pts）（n = 36 pts）（n = 36 pts） 。种群药代动力学分析表明，Primene（R）显着提高了LU-177-二酸的消除速率常数，而不是Lysakare（R）。 Primene（R）还显着使Lutathera（R）血浆暴露（AUC）降低了34％，而Lysakare（R）AUC增加了7％。无论哪种情况，均无肾脏毒性。淋巴细胞减少与AUC显着相关（p = 0.021），其趋势具有更高的lysakare（r）（R）。结论：与Primene（R）不同，Lysakare（R）不会增加LU-177-二酸的消除。这种差异与对AUC的重大影响有关。后一个参数具有较高的室内变异性，但室内变异性较低，这可能对治疗调整具有重要的临床意义。
Background: Lu-177-Dotatate is used in the treatment of somatostatin-receptor-positive inoperable progressive gastroenteropancreatic neuroendocrine tumors. A co-infusion of amino acids (AAs) is administered to prevent renal toxicity.Objective: This study aimed to quantify the impact of two types of AA cocktails on the pharmacokinetics and toxicity of Lu-177-Dotatate.Methods: Four injections of 7400 MBq Lu-177-Dotatate were given per patient with administration of either Primene (R) 10% (containing a cocktail of 20 AAs with 22g of Lysine and 16.8 g of Arginine) or Lysakare (R) (containing 25 g of Lysine and 25 g of Arginine). Nine blood samples were collected at each cycle. Radioactivity-time data were analyzed according to a population-based model using NONMEM (version 7.4.1). Renal and hematological toxicity was evaluated after each cycle.Results: 1,678 Lu-177-Dotatate plasma concentrations versus time were analyzed from 83 consecutive patients with Primene (R) (n= 45 pts) or Lysakare (R) (n= 36 pts). Population pharmacokinetic analysis showed that Primene (R) significantly increased the elimination rate constant of Lu-177-Dotatate as opposed to Lysakare (R). Primene (R) also significantly lowered Lutathera (R) plasma exposure (AUC) by 34%, whereas Lysakare (R) increased AUC by 7%. There was no renal toxicity in either case. Lymphopenia significantly correlated with AUC (p=0.021) with a trend towards higher toxicity with Lysakare (R).Conclusion: Unlike Primene (R), Lysakare (R) does not increase Lu-177-Dotatate elimination. This difference is associated with a significant impact on AUC. The latter parameter has a high interpatient variability but a low intrapatient variability, which could have important clinical implications for treatment tailoring.