5-氟尿嘧啶不同给药途径的药代动力学研究和临床应用

INVESTIGATION OF PHARMACOKINETICS AND CLINICAL APPLICATION OF 5 FLUOROURACIL ADMINISTERED BY THREE DIFFERENT ROUTES

目的：研究５氟尿嘧啶（５Ｆｕ）腹腔、静脉和灌胃３种给药途径化疗的优劣。方法：采用高效液相色谱法比较研究了家兔５Ｆｕ３种给药途经的药代动力学。结果：大剂量腹腔给药能在腹腔，门静脉及肝脏提供高浓度药物，且维持时间较长。静脉给药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，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，但吸收极不规则，个体差异较大。组织中药物浓度测定发现，腹腔给药后，肝脏中药物浓度最高，肾脏浓度最低，而静脉给药则肾脏浓度最高。临床应用结果显示：腹腔化疗组的全身毒副作用明显较静脉化疗组减轻；两组化疗期间均未出现严重并发症。腹腔给药５Ｆｕ１０００ｍｇ／ｄ是安全的。结论：对胃肠道恶性肿瘤术后腹腔内复发和肝转移的防治，腹腔化疗是一种较为理想的术后辅助化疗措施。

OBJECTIVE:The aim of this experiment was to observe the effects of intraperitoneal(ip),intraveinous(iv)and intragastric(ig) administration.METHODS:Pharmacokinetic comparison of 5 fluorouracil(5 Fu)administerd ip,iv and ig was made in rabbits by HPLC method.RESULTS:ip administration of 5 Fu could maintain high,stable and sustained concentration in the peritoneal cavity,portal vein and liver while sparing the systemic blood.After iv administration of 5 Fu,drug concentration in systemic blood and portal vein was very high.Sustainmen of concentration was relatively of short duration.After igadministration the concentration of 5 Fu in portal vein was higher than that in systemic blood.But absorption of 5 Fu was irregular.There was a high difference in the individuals.The results of the clinical application showed that the toxicity and side effect of iv administration was obviously higher than that of ip administration.It is security that 5 Fu 1 000 mg was used in a day.CONCLUSION:ip chemotherapy has a significant pharmacokinetic advantage over the convention iv and ig routes after surgery for gastrointestinal malignancies.