快樂小藥師 Im pharmacist nichts glücklich

今天發生了一件事情，就是有人不小心將Paclitaxel裝進了一般的輸液套，這時候到底會發生什麼事情呢？

平常，亞培是會附上一個專用的輸液套，至於會這樣做的理由很簡單，因為一般PVC容器的可塑劑大多是使用DEHP，然而有研究指出當PVC容器內是脂溶性的溶劑時，其可塑劑(尤以DEHP)會被溶離出來；Paclitaxel 不溶於水，其製劑中加入Cremophor ®EL (Alcoholic polyoxyethylated castor oil)及dehydrated alcohol來增加它的溶解度，當Paclitaxel置於PVC的容器或管線時，DEHP會明顯被溶離出來，但使用玻璃或polyoefin 材質的容器及polyethylene 材質的sets時並不會有此現象，因此建議Taxol的輸注容器應選用玻璃或polyoefin 材質的容器及polyethylene 材質的sets，以減少可塑劑DEHP對人體的傷害。

之前有看過的研究顯示Taxol注射液經由5%葡萄糖注射液或0.9% NaCl注射液調配成1.2mg/ml的濃度，置於PVC (Polyvinyl Chloride)袋中，分別在1、2、4、及8小時萃取DEHP(Diethylhexyl Phthalate) 的量，大約是在50-208mcg/ml之間。用0.9%的NaCl注射液調配成1.2mg/ml，置於20-22℃下，在第八小時，萃取DEHP的量最高，達到83mcg/ml。經萃取收集的DEHP；在任何一種品牌的PVC容器，其DEHP的含量會隨著時間而增加。Paclitaxel稀釋液置於PVC袋中，萃取出的DEHP是Docetaxel的2-8倍以上。(Mazzo et al. 1997)

長期的安定性方面，Taxol以5%葡萄糖注射液其含有無菌、脫水酒精(酒精濃度是20%或25%)，稀釋成1mg/ml的混合液，與一般調配的混合液比較，最少可維護7天的物理安定性。長期的安定性方面，1mg/ml Taxol溶液(含有25%酒精)其可以去維持28天的低濃度之細菌、酵母菌及黴菌的Antimicrobial Preservatives Effectiveness Test；如此可證明長時間持續輸注液中，只會有低可能性的污染。(Trissel et al, 1997)

在安定性研究方面指出，Taxol若以5%葡萄糖注射液或0.9% NaCl注射液稀釋成0.3-1.2 mg/ml ，在室溫下的安定性可維持24小時(Waugh et al,1991)。調配後的Taxol溶液應置於玻璃或non-PVC的容器內；使用時要經由孔徑不超過0.22μ之管線內多微孔濾膜。

另外在oncology nursing forum的January 2005, Volume 32, Number 1裡面的這篇：Avoiding Carcinogen Exposure With Intraperitoneal Paclitaxel有介紹，節錄發現及結論給大家參考：

Findings: The in vitro studies showed that a solution of 40 mg paclitaxel dissolved in a 1 liter bag of Dianeal resulted in the extraction of approximately 26 mg DEHP over 24 hours. Approximately 2 mg DEHP was leached during the first hour and approximately 1 mg per hour over the following 23 hours. Equivalent results were obtained when 20 mg paclitaxel was dissolved in a 500 ml bag of 6% hetastarch (Hespan®) with a leaching of approximately 13 mg DEHP in 24 hours. Using the same paclitaxel concentration, the chronic ambulatory peritoneal dialysis solution transfer tubing with a total capacity of 10 ml produced approximately 2 mg DEHP over 24 hours, of which approximately 0.5 mg was produced during the first four hours. Samples from a single patient showed that immediately prior to administration, a 1 liter bag of Dianeal containing 34 mg paclitaxel had about 3.3 mg DEHP. Approximately 3% (110 mcg) of unchanged DEHP was recovered from the peritoneal fluid at 24 hours. Total DEHP excreted in urine over the 24-hour period was approximately 900 mcg (27%).

Conclusion: This study showed that the carcinogen DEHP is leached after preparation of paclitaxel from PVC-based containers and DEHP constantly accumulates in the solution transfer tubing.

所以千萬要小心，不要加錯了。