Kamei Koichi, Sako Mayumi, Ishikawa Tomoaki, Sato Mai, Ogura Masao, Uno Teruaki, Kiyotani Chikako, Mori Tetsuya, Tanaka Hideaki, Ito Shuichi, Nakamura Hidefumi
Department of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan.
Division for Clinical Trials, Department of Development Strategy, Center for Social and Clinical Research, National Research Institute for Child Health and Development, National Center for Child Health and Development, Tokyo, Japan.
Ther Apher Dial. 2015 Oct;19(5):491-6. doi: 10.1111/1744-9987.12302. Epub 2015 Apr 27.
There have been few reports of carboplatin-based chemotherapy for anuric infants. As we had a chance to treat a one-year-old anuric hepatoblastoma patient with carboplatin, we performed a pharmacokinetic analysis and examined the optimal treatment strategy. A one-year-old anuric boy under peritoneal dialysis was diagnosed with hepatoblastoma. Surgical resection was performed, and administration of carboplatin was scheduled postoperatively aiming at 5 mg·min/mL of the area under the curve from the time of dosing to the time of the last observation (AUC(0-t)). We set the initial dose at 50 mg, higher than that calculated by the Calvert formula (34 mg); the time from the end of carboplatin infusion to the initiation of hemodialysis at 2 h; and the hemodialysis duration at 24 h. The actual AUC0-t was 3.05 mg·min/mL because the elimination half-lives before and during hemodialysis were shorter than expected. The AUC(0-t) after the second dose (100 mg) and the third dose (80 mg) were 7.00 and 4.68 mg·min/mL, respectively. The Calvert formula is not suitable for hemodialysis patients because removal of platinum by hemodialysis is not taken into account. It appears that extrarenal clearance in anuric infants is different from that in adults. We obtained an optimal AUC(0-t) using a dose of 80 mg (200 mg/m(2)), setting the time from the end of carboplatin infusion to the initiation of hemodialysis at 2 h, and performing 8-h hemodialysis. Further accumulation of the pharmacokinetic data of carboplatin is necessary for anuric children.
关于以卡铂为基础的化疗用于无尿婴儿的报道很少。由于我们有机会用卡铂治疗一名一岁的无尿肝母细胞瘤患者，我们进行了药代动力学分析并研究了最佳治疗策略。一名接受腹膜透析的一岁无尿男孩被诊断为肝母细胞瘤。进行了手术切除，并计划术后给予卡铂，目标是从给药时到最后一次观察时的曲线下面积（AUC(0-t)）达到5 mg·min/mL。我们将初始剂量设定为50 mg，高于根据卡尔弗特公式计算的剂量（34 mg）；卡铂输注结束至开始血液透析的时间为2小时；血液透析持续时间为24小时。由于血液透析前和透析期间的消除半衰期比预期短，实际的AUC0-t为3.05 mg·min/mL。第二剂（100 mg）和第三剂（80 mg）后的AUC(0-t)分别为7.00和4.68 mg·min/mL。卡尔弗特公式不适用于血液透析患者，因为未考虑血液透析对铂的清除作用。看来无尿婴儿的肾外清除率与成人不同。我们通过使用80 mg（200 mg/m(2)）的剂量，将卡铂输注结束至开始血液透析的时间设定为2小时，并进行8小时的血液透析，获得了最佳的AUC(0-t)。对于无尿儿童，有必要进一步积累卡铂的药代动力学数据。
