5-氟尿嘧啶不同给药途径的药代动力学研究和临床应用

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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: To study the advantages and disadvantages of 5 kinds of administration routes of 5-fluorouracil (5Fu) intraperitoneal, intravenous and intragastric administration. Methods: The pharmacokinetics of 5  Fu 3 routes of administration in rabbits were compared by high performance liquid chromatography. Results: High-dose intraperitoneal administration can provide high concentration of drugs in the abdominal cavity, portal vein and liver, and maintain a longer time. Intravenous administration of plasma concentration and portal vein plasma concentrations were higher, but the effective plasma concentration maintenance time is short, intragastric administration, the peritoneal fluid concentration is very low, although the portal vein blood concentration higher than the surrounding blood, but the absorption Very irregular, individual differences. Tissue drug concentration determination found that, after intraperitoneal administration, the highest drug concentration in the liver, the lowest kidney concentration, and intravenous administration of the highest concentration of the kidneys. The results of clinical application showed that the systemic toxicity and side effects in intraperitoneal chemotherapy group were significantly lower than those in intravenous chemotherapy group. No serious complications occurred in both groups during chemotherapy. Intraperitoneal administration of 5  Fu1000mg / d is safe. Conclusion: Prevention and treatment of postoperative intra-abdominal recurrence and liver metastasis of gastrointestinal malignant tumor, intraperitoneal chemotherapy is an ideal postoperative adjuvant chemotherapy.
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