Topical absorption and inactivation of cytotoxic anticancer agents in vitro.
Topical absorption and inactivation of cytotoxic anticancer agents in vitro.
复制标题
细胞毒性抗癌剂的体外局部吸收和灭活。
作者：
Robert T. Dorr;David S. Alberts
背景
细胞毒性抗癌剂可能对为癌症患者制备或给药的人员造成致癌或致畸风险。
方法
进行了一系列实验室研究，以量化各种细胞毒性抗癌剂的经皮吸收和局部灭活程度。使用艾姆斯细菌致突变性试验和反相高效液相色谱测量评价了蒽环类药物和蒽DNA嵌入剂的局部灭活。
结果
在体外暴露于100 μ g柔红霉素、阿霉素和美法仑24小时后，通过人腹部皮肤的药物水平可忽略不计，通常低于1 - 5 ng/ml的高效液相色谱灵敏度限值（小于或等于0.001%的可能吸收）。美法仑粉末可从用于手动粉碎14片2 mg片剂的研钵和研杵附近的空气中回收;超过12英寸，空气传播的药物不可回收。一个标准浓度（4%）的次氯酸钙完全灭活蒽环类药物柔红霉素和阿霉素，但米托蒽醌。该试剂需要在432毫克的次氯酸钙浓度下处理以完全灭活。
结论
总之，局部细胞毒性药物吸收可忽略不计（如果发生）。然而，口服制剂的机械操作可能存在暴露于空气传播的药物颗粒的风险。浓缩的次氯酸钙在局部灭活某些致癌的细胞毒性剂方面非常有效。
BACKGROUND
Cytotoxic anticancer agents may pose carcinogenic or teratogenic risks to personnel who prepare or administer drugs to patients with cancer.
METHODS
A series of laboratory studies were done to quantify the extent of percutaneous absorption and topical inactivation for various cytotoxic anticancer agents. Topical inactivation of anthracyclines and anthracene DNA intercalating agents was evaluated using Ames bacterial mutagenicity assays and reverse-phase high-performance liquid chromatography measurements.
RESULTS
Drug levels passing through human abdominal skin exposed in vitro for 24 hours to 100 micrograms of daunorubicin, doxorubicin, and melphalan were negligible and typically less than the high-performance liquid chromatography sensitivity limit of 1-5 ng/ml (less than or equal to 0.001% possible absorption). Melphalan powder was recoverable from the air near a mortar and pestle used to crush 14 2-mg tablets manually; beyond 12 inches, no airborne drug was recoverable. A standard (4%) concentration of calcium hypochlorite completely inactivated the anthracyclines daunorubicin and doxorubicin but not mitoxantrone. This agent required treatment at a calcium hypochlorite concentration of 432 milligrams for complete inactivation.
CONCLUSIONS
In summary, topical cytotoxic drug absorption is negligible (if it occurs at all). However, mechanical manipulations of oral formulations may present a risk of exposure to airborne drug particles. Concentrated calcium hypochlorite is extremely effective in the the topical inactivation of certain carcinogenic cytotoxic agents.