5－氟尿嘧啶三种给药途径的药代动力学研究

Pharmacokinetics investigation of 5-fluorouracil through three routes of administration

采用高效液相色谱法比较研究了家兔５－ＦＵ腹腔、静脉和灌胃３种给药途径的药代动力学。结果显示：大剂量腹腔给药能在腹腔、门静脉及肝脏提供高浓度药物，且维持时间长，消除半衰期（ｔ１／２β）分别为（３．８１±０．１４）ｈ和（１．２８±０．０９）ｈ，而周围血药浓度极低；静脉给药后周围血药浓度及门静脉血药浓度均较高，但有效血药浓度维持时间短，ｔ１／２β分别为（０．７１４±０．０２）ｈ和（０．６６８±０．０４）ｈ，灌胃给药后，腹腔液药浓度极低，门静脉血药浓度虽然高于周围血，但吸收不规则，个体差异较大。组织中药浓度测定发现，腹腔给药后，肝脏中药浓度最高，肾脏浓度最低，而静脉给药则肾脏浓度最高。提示：对胃肠道恶性肿瘤术后腹腔内复发和肝转移的防治，腹腔化疗较传统的静脉化疗和口服给药途径为优。

Pharmacokinetic comparison of 5-fluorouracil(5-FU) administered ip, iv and ig was made in rabbits with HPLC method.Ip administration of 5-FU could keep highly stable and sustained high concentration in the peritoneal cavity, portal vein and liver, while sparing the systemic blood. t1/2β was (3. 81±0. 14) h and(1.28±0. 09) h. After iv administration of 5-FU, the drug concentration in systemic blood and portal vein blood was very high. The concentration sustained was of relatively short duration. t1/2β was(0. 71±0. 02)h and (0. 67±0.04) h. After ig administration, the concentration of 5-FU in portal was higher than that in systemic blood. The absorption of 5-FU was irregular, There were great differences among the individuals. It is believed that ip chemotherapy has a significant pharmacokinetic advantage.over the conventional iv and ig routes after surgery for gastrointestinal malignancies.