Stability in vitro and antitumor activity in vivo of preparations of 5-Fu mixed with parenteral nutrition solution

LIU Guangxuan; ZHAO Qian; SUI Yue; GUAN Dingyue; SUN Bo; ZHU Dantong; QI Xianfu

doi:10.3969/j.issn.1002-266X.2016.44.003

Abstract：Objective To observe the compatible stability in vitro and antitumor activity in vivo of preparations of 5-fluorouracil (5-Fu) mixed with total parenteral nutrition (TPN) solution (5-Fu and TPN solution) and to provide the basis for its clinical application .Methods The blank parenteral nutrition solution and 5-Fu and TPN solution were mixed at room temperature for 24 h.The appearances were observed and the mean diameter ( MD) and coefficient of variation ( CV) of fat particles , pH value and osmotic pressure was evaluated .The stability of 5-Fu in the 5-Fu and TPN solution was deter-mined by HPLC.The H22 transplanted models of mice were established .Sixty mice were divided into six groups:5-FU-TPN-L (30 mg/kg), 5-FU-TPN-M (65 mg/kg), 5-FU-TPN-H (130 mg/kg), 5-FU-NS (65 mg/kg), TPN and the con-trol group, each group had 10 mice.On the day 3 after being inoculated with H22 tumor cells, the mice in the six groups were intraperitoneally injected with the above six kinds of liquids , separately, once every other day for 5 times.On day 2 after the last administration , mice were killed and antitumor rate was calculated .Results Compared with the blank paren-teral nutrition solution, there were no significant changes in the appearances , MD, CV, pH value, osmotic pressure and the contents of 5-Fu within 24 h of 5-Fu and TPN solution (all P>0.05).The antitumor rates of the 5-FU-TPN-L, 5-FU-TPN-M, 5-FU-NS, and TPN groups were 24.3%, 91.8%, 78.7% and 14.6%, the antitumor rate of the 5-FU-TPN-M and 5-FU-NS groups were higher than those of the 5-FU-TPN-L and TPN groups, and the antitumor rate of 5-FU-TPN-M group was higher than that of the 5-FU-NS group, significant difference was found between every two groups ( all P <0.01).The toxicity of 5-FU-TPN-H was strong, and 6 mice died, so no statistics were carried out.Conclusion 5-Fu in TPN solution is stable within 24 h and the antitumor effect of 5-Fu at 65 mg/mL is better than single administration of 5-Fu.