Radford J A, Margison J M, Swindell R, Lind M J, Wilkinson P M, Thatcher N
CRC Department of Medical Oncology, Christie Hospital, Manchester, UK.
J Cancer Res Clin Oncol. 1991;117 Suppl 4(Suppl 4):S154-6. doi: 10.1007/BF01613222.
Dose fractionation is known to reduce the toxicity of ifosfamide and also results in an increased production of alkylating metabolites. Administration by slow infusion using the convenience of ambulatory pumps is therefore of interest. We used HPLC to investigate the stability of ifosfamide in aqueous solution (either alone, solution A, or mixed with mesna, solution B) under various conditions over a 9-day period. At both ambient temperature in daylight and 27 degrees C in a dark environment, there was no evidence of ifosfamide decay in either solution. However, at 37 degrees C in a dark environment, a fall was detected in both solutions, which at 9 days amounted to a loss of 7% of the amount of ifosfamide present at time zero. At 70 degrees C, levels of ifosfamide in both solutions fell within 72 h to markedly lower levels than controls, thus confirming that the methods used were indicative of stability. We conclude that ifosfamide, either alone or mixed with mesna, is stable for 9 days at temperatures up to 27 degrees C; even at 37 degrees C, the measured loss is small. The continuous infusion of ifosfamide over 7 days by ambulatory pump is now a practical proposition.
已知剂量分割可降低异环磷酰胺的毒性,还会导致烷基化代谢产物生成增加。因此,利用便携式输液泵方便地进行缓慢输注给药很有意义。我们使用高效液相色谱法研究了异环磷酰胺在水溶液中(单独的溶液A或与美司钠混合的溶液B)在各种条件下9天内的稳定性。在日光下的环境温度以及黑暗环境中的27摄氏度条件下,两种溶液中均未发现异环磷酰胺降解的迹象。然而,在黑暗环境中的37摄氏度条件下,两种溶液中的异环磷酰胺均出现下降,到第9天时,下降幅度相当于初始时异环磷酰胺含量的7%。在70摄氏度时,两种溶液中的异环磷酰胺水平在72小时内降至明显低于对照的水平,从而证实所采用的方法能够表明稳定性。我们得出结论,异环磷酰胺单独使用或与美司钠混合,在高达27摄氏度的温度下可稳定9天;即使在37摄氏度时,测得的损失也很小。现在,通过便携式输液泵连续输注异环磷酰胺7天是可行的方案。