Paál K, Horváth J, Csáki C, Ferencz T, Schuler D, Borsi J
Semmelweis Orvostudományi Egyetem, Budapest, II. sz. Gyermekklinika.
Orv Hetil. 1996 Oct 13;137(41):2257-61.
High dose (5 g/m2/24 h) methotrexate therapy was combined two times with etoposide (100 mg/m2/1h) infusions as a part of the Medulloblastoma protocol developed in our Department Vepesid therapy was administered in two different schedules. The first group of the patients have received etoposide immediately before and at the end (24th h) of methotrexate treatment. The second group was treated with etoposide at 24 h and at 48 hour after starting methotrexate infusion. In this latter group treatment related grade 3-4 toxicity developed more frequently than in the first group (58.6% vs 33.3%). The authors observed that after the second dose of etoposide given at 48 h (second group) both total and unbound serum methotrexate levels (determined by high performance liquid chromatography) were elevated by 53.14-109.19%, and 25.86-64.95%, respectively by the third hour after completion of Vepesid infusion. This effect was detectable for 6 hours. All the liver and kidney functions of the patients were in the normal range. These results suggest the possibility of partial recirculation of extra/intracellular methotrexate into the blood after etoposide administration. Based on these results the therapeutic protocol has been modified and Vepesid is given prior to and at the end (24 h) of high dose methotrexate treatment. Under these conditions only a slight decrease of methotrexate elimination has been detected between the 25-28th h. These results emphasize the role of possible schedule dependent interactions of cytostatic drugs.
高剂量（5克/平方米/24小时）甲氨蝶呤疗法与依托泊苷（100毫克/平方米/1小时）输注联合使用了两次，作为我们科室制定的髓母细胞瘤治疗方案的一部分。依托泊苷治疗采用了两种不同的给药方案。第一组患者在甲氨蝶呤治疗前及治疗结束时（第24小时）立即接受依托泊苷治疗。第二组在甲氨蝶呤输注开始后24小时和48小时接受依托泊苷治疗。在后一组中，与治疗相关的3 - 4级毒性比第一组更频繁地出现（58.6%对33.3%）。作者观察到，在第二组患者于48小时给予第二剂依托泊苷后，依托泊苷输注完成后第三小时，血清甲氨蝶呤总水平和游离水平（通过高效液相色谱法测定）分别升高了53.14 - 109.19%和25.86 - 64.95%。这种效应可持续6小时。所有患者的肝肾功能均在正常范围内。这些结果表明，依托泊苷给药后，细胞外/细胞内甲氨蝶呤可能部分再循环进入血液。基于这些结果，治疗方案已被修改，依托泊苷在高剂量甲氨蝶呤治疗前及治疗结束时（24小时）给予。在这些条件下，仅在第25 - 28小时之间检测到甲氨蝶呤清除率略有下降。这些结果强调了细胞毒性药物可能存在的给药方案依赖性相互作用的作用。
