PDF(Pubmed)
Abstract：
OBJECTIVE: Chemotherapy-induced nausea and vomiting (CINV) are common side effects in pediatric oncology treatment. Besides 5-HT3-antagonists, both dexamethasone and aprepitant are cornerstone drugs in controlling these side effects. Based on results of adult studies, the dexamethasone dose is reduced by 50% when combined with aprepitant, because of a drug-drug interaction, even though data on the interaction in children is lacking. The current study was developed to investigate the effect of aprepitant on dexamethasone clearance (CL) in children, in order to assess if dexamethasone dose reduction for concomitant use of aprepitant is appropriate in the current antiemetic regimen.
METHODS: In total, 65 children (0.6-17.9 years), receiving intravenous or oral antiemetic therapy (dexamethasone ± aprepitant) as standard of care, were included. 305 dexamethasone plasma concentrations were determined using LC-MS/MS. An integrated dexamethasone and aprepitant pharmacokinetic model was developed using non-linear mixed effects modelling in order to investigate the effect of aprepitant administration on dexamethasone CL.
RESULTS: In this population, dexamethasone CL in patients with concomitant administration of aprepitant was reduced by approximately 30% of the uninhibited CL (23.3 L/h (95% confidence interval 20.4-26.0)). This result is not consistent with the results of adult studies (50% reduction). This difference was not age dependent, but might be related to the route of administration of dexamethasone. Future studies are needed to assess the difference in oral/intravenous dexamethasone.
CONCLUSIONS: When dexamethasone is given intravenously as a component of triple therapy to prevent CINV in children, we advise to reduce the dexamethasone dose by 30% instead of 50%.
METHODS: In total, 65 children (0.6-17.9 years), receiving intravenous or oral antiemetic therapy (dexamethasone ± aprepitant) as standard of care, were included. 305 dexamethasone plasma concentrations were determined using LC-MS/MS. An integrated dexamethasone and aprepitant pharmacokinetic model was developed using non-linear mixed effects modelling in order to investigate the effect of aprepitant administration on dexamethasone CL.
RESULTS: In this population, dexamethasone CL in patients with concomitant administration of aprepitant was reduced by approximately 30% of the uninhibited CL (23.3 L/h (95% confidence interval 20.4-26.0)). This result is not consistent with the results of adult studies (50% reduction). This difference was not age dependent, but might be related to the route of administration of dexamethasone. Future studies are needed to assess the difference in oral/intravenous dexamethasone.
CONCLUSIONS: When dexamethasone is given intravenously as a component of triple therapy to prevent CINV in children, we advise to reduce the dexamethasone dose by 30% instead of 50%.
摘要：
目的：化疗引起的恶心呕吐（CINV）是儿科肿瘤治疗中常见的副作用。除了5-HT3-拮抗剂,地塞米松和阿瑞吡坦都是控制这些副作用的基础药物.根据成人研究的结果，与阿瑞匹坦合用时，地塞米松剂量减少50%，因为药物-药物的相互作用，尽管缺乏关于儿童互动的数据。本研究旨在研究阿瑞匹坦对儿童地塞米松清除率（CL）的影响，为了评估在当前的止吐方案中同时使用阿瑞吡坦时减少地塞米松剂量是否合适。
方法：总共，65名儿童（0.6-17.9岁），接受静脉或口服止吐治疗（地塞米松±阿瑞吡坦）作为标准护理，包括在内。使用LC-MS/MS测定305地塞米松血浆浓度。使用非线性混合效应模型建立了地塞米松和阿瑞匹坦的综合药代动力学模型，以研究阿瑞匹坦给药对地塞米松CL的影响。
结果：在这个人群中，同时给予阿瑞吡坦的患者的地塞米松CL降低了未抑制CL的约30%(23.3L/h(95%置信区间20.4-26.0)).该结果与成人研究的结果(减少50%)不一致。这种差异与年龄无关，但可能与地塞米松的给药途径有关。未来的研究需要评估口服/静脉注射地塞米松的差异。
结论：当静脉注射地塞米松作为三联疗法的组成部分，以预防儿童CINV时，我们建议将地塞米松剂量减少30%，而不是50%。
方法：总共，65名儿童（0.6-17.9岁），接受静脉或口服止吐治疗（地塞米松±阿瑞吡坦）作为标准护理，包括在内。使用LC-MS/MS测定305地塞米松血浆浓度。使用非线性混合效应模型建立了地塞米松和阿瑞匹坦的综合药代动力学模型，以研究阿瑞匹坦给药对地塞米松CL的影响。
结果：在这个人群中，同时给予阿瑞吡坦的患者的地塞米松CL降低了未抑制CL的约30%(23.3L/h(95%置信区间20.4-26.0)).该结果与成人研究的结果(减少50%)不一致。这种差异与年龄无关，但可能与地塞米松的给药途径有关。未来的研究需要评估口服/静脉注射地塞米松的差异。
结论：当静脉注射地塞米松作为三联疗法的组成部分，以预防儿童CINV时，我们建议将地塞米松剂量减少30%，而不是50%。
