Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, 52, Hyochangwon-gil, Yongsan-Gu, Seoul, 140-742, Korea.
Cancer Chemother Pharmacol. 2014 May;73(5):1041-5. doi: 10.1007/s00280-014-2439-3. Epub 2014 Mar 18.
Today, cancer incidence during pregnancy is increasing as women delay childbearing until later in life. Therefore, chemotherapy is regularly administered in pregnant women with cancer. In the present study, we evaluated the change in the pharmacokinetics and the fetus distribution of paclitaxel during pregnancy using pregnant rats.
Pharmacokinetic parameters, placenta, and brain transport of [(3)H]paclitaxel were investigated in nonpregnant or pregnant rats using single intravenous injection technique.
The plasma pharmacokinetics of paclitaxel in pregnant rats was markedly different compared with nonpregnant rats. The V dss and CL of paclitaxel in pregnant rats were increased, and AUC was decreased compared with nonpregnant rats. The fetus uptake of paclitaxel is markedly lower than the placenta uptake. Paclitaxel is a substrate of P-glycoprotein (P-gp), so P-gp would affect the transport of paclitaxel to the fetus. The brain uptake of [(3)H]paclitaxtel was about twofold lower than that of nonpregnant rats.
Current findings are important when considering cancer treatment with paclitaxel during pregnancy.
随着女性生育年龄推迟，如今妊娠期间癌症的发病率不断上升。因此，临床上常对妊娠合并癌症患者进行化疗。本研究旨在通过妊娠大鼠评估紫杉醇在妊娠期间的药代动力学变化及其向胎儿的分布。
采用单次静脉注射技术，研究了非妊娠和妊娠大鼠体内 [(3)H]紫杉醇的药代动力学参数、胎盘和脑转运。
与非妊娠大鼠相比，妊娠大鼠体内紫杉醇的血浆药代动力学明显不同。与非妊娠大鼠相比，妊娠大鼠的 V dss 和 CL 增加，AUC 降低。胎儿对紫杉醇的摄取明显低于胎盘对紫杉醇的摄取。紫杉醇是 P-糖蛋白（P-gp）的底物，因此 P-gp 会影响紫杉醇向胎儿的转运。 [(3)H]紫杉醇在脑内的摄取量约为非妊娠大鼠的两倍。
当考虑在妊娠期间使用紫杉醇进行癌症治疗时，这些发现非常重要。
