摘要
目的:测定不同途径5-氟尿嘧啶(5-fluorouracil,5-FU)化疗后家兔门静脉血及肝脏组织中的药物浓度.方法:以家兔为模型动物分别进行5-FU静脉化疗、腹腔化疗和缓释化疗,用高效液相色谱法测定门静脉血及组织中5-FU浓度.根据各组门静脉血药浓度-时间曲线,计算曲线下面积(area under the concentration-time curve,AUC).结果:静脉组血药浓度在给药后即刻达到峰值,15min仍高达47.89g/mL,但仅能维持4h;腹腔组给药后15min达到血药浓度峰值(20.67g/mL),维持时间较静脉组稍长,可达到24h;缓释组在给药后2h达到最高值0.82g/mL,且持续时间较长,16d后仍可检测到.3组血药浓度AUC依次升高,分别为21.57g/(mL·h)、42.85g/(mL·h)和70.08g/(mL·h).同时,缓释组各组织5-FU浓度消除显著减慢,给药12d后肝组织中仍可测到,腹腔组组织药物浓度仅维持至给药后24h.结论:5-FU腹腔内缓释化疗可显著延长门静脉血及肝脏组织中5-FU持续时间,有助于增强化疗效果.
AIM： To determine the concentration of 5-fluorouracil （5-FU） in the portal vein blood and liver in a rabbit model after chemotherapy with 5-FU given via different routes of administration. METHODS： The portal vein blood and liver biopsy were collected at different time points after intravenous chemotherapy, intraperitoneal chemotherapy or intraperitoneal sustained-releasing chemotherapy with 5-FU. The concentration of 5-FU was measured by HPLC. The area under the concentration-time curve （AUC） was calculated based on the concentration-time curve. RESULTS： The concentration of 5-FU in the portal vein reached the peak （0.82 μg/mL） two hours after intraperitoneal administration of sustained-releasing agents. The concentration of5-FU in the portal vein was stable and the drug could be detected until day 16 after treatment. In contrast, the average concentration of 5-FU in the portal vein of animals receiving intraperitoneal injection of 5-FU was 20.67 μg/mL 15 minutes after injection and the drug was undetectable 24 h later. 5-FU in the portal vein of animals receiving intravenous chemotherapy was undetectable 4 h later. AUC in the intravenous, intraperitoneal and sustained-releasing groups was 21.57 μg/（mL.h）, 42.85 μg/（mL. h） and 70.08 μg/（mL.h）, respectively. 5-FU in liver biopsy could be detected until day 12 after intraperitoneal administration of sustainedreleasing agents. In contrast, 5-FU in liver biopsy was undetectable 24 h later in animals receiving intraperitoneal injection of 5-FU.
CONCLUSION： Intr.aperitoneal sustainedreleasing chemotherapy may prolong the effective exposure time of 5-FU in the portal vein and enhance chemotherapeutic effects in the liver.
出处
《世界华人消化杂志》
CAS
北大核心
2013年第22期2176-2180,共5页
World Chinese Journal of Digestology
关键词
5-氟尿嘧啶
缓释剂
色谱法
5-Fluorouracil
Delayed-action preparations
Chromatography
