Department of Internal Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Germany.
Br J Clin Pharmacol. 2010 Dec;70(6):903-7. doi: 10.1111/j.1365-2125.2010.03792.x.
The objective of this investigation was to assess the effect of aprepitant on the pharmacokinetics of high-dose melphalan used as conditioning therapy before blood stem cell transplantation in multiple myeloma.
Aprepitant (125 mg) or placebo was administered 1 h before melphalan therapy (1 h infusion of 100 mg m⁻²). Eleven plasma samples were obtained over 8 h and melphalan was quantified using an LC/MS/MS method. Standard pharmacokinetic parameters were calculated and nonparametric testing was applied to assess the differences between aprepitant and placebo treatment.
Twenty patients received placebo and 10 patients aprepitant treatment. There were no differences observed for C(max) at the end of melphalan infusion (placebo 3431 ± 608 ng ml⁻¹ vs. aprepitant 3269 ± 660 ng ml⁻¹). In addition, AUC and terminal elimination half-life were not changed by aprepitant. Total clearance of melphalan was 304 ± 58 ml min⁻¹ m⁻² (placebo) which was not influenced by aprepitant (288 ± 78 ml min⁻¹ m⁻²).
The administration of the NK₁ receptor antagonist aprepitant 1 h before a high-dose chemotherapy does not influence the exposure and the elimination of melphalan. Therefore, oral administration of 125 mg aprepitant 1 h before melphalan infusion does not alter the disposition of intravenously administered melphalan.
本研究旨在评估阿瑞匹坦对多发性骨髓瘤患者进行造血干细胞移植前大剂量美法仑预处理时美法仑药代动力学的影响。
阿瑞匹坦（125mg）或安慰剂在美法仑治疗前 1 小时（100mg/m²，1 小时输注）给药。在 8 小时内采集 11 份血浆样本，并采用 LC/MS/MS 法定量美法仑。计算标准药代动力学参数，并采用非参数检验评估阿瑞匹坦与安慰剂治疗的差异。
20 例患者接受安慰剂治疗，10 例患者接受阿瑞匹坦治疗。在美法仑输注结束时（安慰剂 3431±608ng/ml 与阿瑞匹坦 3269±660ng/ml），Cmax 无差异。此外，AUC 和末端消除半衰期不受阿瑞匹坦影响。美法仑总清除率为 304±58ml/min/m²（安慰剂），阿瑞匹坦未影响其清除率（288±78ml/min/m²）。
在接受大剂量化疗前 1 小时给予 NK₁ 受体拮抗剂阿瑞匹坦不会影响美法仑的暴露和消除。因此，在美法仑静脉输注前 1 小时给予 125mg 阿瑞匹坦不会改变美法仑的体内分布。
