Division of Pediatric Nephrology, The Children's Mercy Hospital and Clinics, University of Missouri at Kansas City, Kansas City, MO, USA.
Pediatr Nephrol. 2010 Jun;25(6):1185-9. doi: 10.1007/s00467-009-1420-6. Epub 2010 Jan 19.
Cisplatin is a highly effective and frequently used drug in the chemotherapy of solid tumors in children, but there is currently no information to guide dosing in children requiring dialysis. Here, we present the case of a 2-year-old boy with end-stage renal disease managed with peritoneal dialysis and requiring cisplatin for a newly diagnosed hepatoblastoma. A pharmacokinetic study was performed to personalize the cisplatin dose with the goal of providing adequate cisplatin exposure and avoiding excessive exposure and toxicity. Accordingly, 25% of the standard cisplatin dose was infused intravenously over 4 h. Serial blood and peritoneal fluid samples were obtained, and free cisplatin levels were subjected to noncompartmental pharmacokinetic analysis. The disposition of free cisplatin was significantly altered as compared to that of normal children. Despite a 75% dose reduction, our patient showed a fourfold increase in free cisplatin exposure (AUC = 64.1 h mcg/mL) compared with the AUC observed in children with normal kidney (15 + or - 9 h mcg/mL) function. When a subsequent dose was decreased to 8.7% of the standard dose, the free cisplatin AUC measured 29.7 h mcg/mL and more closely approximated the exposure observed in children with normal kidney function.
顺铂是儿童实体瘤化疗中一种非常有效且常用的药物，但目前尚无信息可指导需要透析的儿童的剂量。在这里，我们报告了一例 2 岁男孩的病例，该男孩患有终末期肾病，接受腹膜透析治疗，并因新诊断的肝母细胞瘤需要顺铂治疗。进行了一项药代动力学研究，以个性化顺铂剂量，目标是提供足够的顺铂暴露，避免过度暴露和毒性。因此，静脉输注 4 小时内给予标准顺铂剂量的 25%。连续采集血和腹腔液样本，并对游离顺铂水平进行非房室药代动力学分析。与正常儿童相比，游离顺铂的处置明显改变。尽管剂量减少了 75%，但与正常肾功能儿童观察到的 AUC（15 + - 9 h mcg/mL）相比，我们的患者游离顺铂暴露增加了四倍（AUC = 64.1 h mcg/mL）。当随后的剂量减少到标准剂量的 8.7%时，测量的游离顺铂 AUC 为 29.7 h mcg/mL，更接近正常肾功能儿童观察到的暴露。
