Füger K, Blumenstein M, Sauer H
Medizinische Klinik III, Klinikum Grosshadern der Ludwig-Maximilians-Universität München, BRD.
Onkologie. 1990 Aug;13(4):289-94. doi: 10.1159/000216778.
There are no established guidelines for detoxification for most cases of overdosage or intoxication with cytostatic drugs. Little is known about the dialysability of cytostatic drugs. To obtain further information on the dialysability of cytostatic drugs, human plasma was incubated with cytostatic drugs and dialysed in vitro using "mini-modules" with capillaries identical to clinical use. Cytotoxicity before and after dialysis was measured in a biological test system using permanent human lymphoblast cultures (LS2). The 20 cytostatic drugs studied could be categorised as follows: Good dialysability in vitro: methotrexate, 5-fluorouracil, cytarabine, actinomycin D, mitomycin C, 4-OH-cyclophosphamide, ifosfamide, melphalan, dacarbazine, cisplatin. Intermediate dialysability in vitro: adriamycin, epirubicin, carmustine. Ineffective dialysability in vitro: daunorubicin, vincristine, vinblastine, vindesine, etoposide, teniposide, mitoxantrone. These in vitro results cannot be transferred automatically into the in vivo situation because of specific drug distribution and metabolic rates. Considering pharmacokinetic data, the following recommendations can be made for practical clinical purposes: Detoxification by hemodialysis in vivo: Possibly effective: Methotrexate, 5-fluorouracil, mytomicin C, cyclophosphamide, ifosfamide, melphalan, carmustine, dacarbazine. Ineffective: Adriamycin, epirubicin, daunorubicin, mitoxantrone, actinomycin D, etoposide, teniposide, vincristine, vinblastine, vindesine, cytarabine, cisplatin.
对于大多数细胞毒性药物过量或中毒病例,目前尚无既定的解毒指南。关于细胞毒性药物的可透析性,人们了解甚少。为了获取更多关于细胞毒性药物可透析性的信息,将人血浆与细胞毒性药物一起孵育,并使用与临床应用相同的毛细管的“微型模块”进行体外透析。在使用永久性人类淋巴母细胞培养物(LS2)的生物测试系统中测量透析前后的细胞毒性。所研究的20种细胞毒性药物可分类如下:体外透析性良好:甲氨蝶呤、5-氟尿嘧啶、阿糖胞苷、放线菌素D、丝裂霉素C、4-羟基环磷酰胺、异环磷酰胺、美法仑、达卡巴嗪、顺铂。体外透析性中等:阿霉素、表柔比星、卡莫司汀。体外透析无效:柔红霉素、长春新碱、长春碱、长春地辛、依托泊苷、替尼泊苷、米托蒽醌。由于特定的药物分布和代谢速率,这些体外结果不能自动转化为体内情况。考虑到药代动力学数据,出于实际临床目的,可提出以下建议:体内血液透析解毒:可能有效:甲氨蝶呤、5-氟尿嘧啶、丝裂霉素C、环磷酰胺、异环磷酰胺、美法仑、卡莫司汀、达卡巴嗪。无效:阿霉素、表柔比星、柔红霉素、米托蒽醌、放线菌素D、依托泊苷、替尼泊苷、长春新碱、长春碱、长春地辛、阿糖胞苷、顺铂。