论文部分内容阅读
目的:观察研究5-氟尿嘧啶腹腔、静脉和灌胃三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-氟尿嘧啶腹腔、静脉和灌胃化疗三种给药途径的药代动力学。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,腹腔液和门静脉的消除半衰期(T_(1/2)β)分别为3.81±0.14 h 和1.28±0.09 h,而周围血药浓度极低,腹腔液及门静脉药峰浓度分别为股静脉的206倍和6.7倍。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,T_(1/2)β分别为0.71±0.02 h 和0.67±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,但吸收极不规则,个体差异较大。组织中药浓度测定发现,腹腔给药后,肝脏中的药浓度最高,肾脏浓度最低,而静脉给药则肾脏浓度最高。结论:这些药代动力学特点提示,对胃肠道恶性肿瘤术后腹腔内复发和肝转移的防治,腹腔化疗将远较传统的静脉化疗和口服给药为优。是一种较为理想的术后辅助化疗措施,可作为一种常规措施用于胃肠道肿瘤术后化疗。
Objective: To study the advantages and disadvantages of three chemotherapy routes of intraperitoneal, intravenous and intragastric administration of 5-Fluorouracil. Methods: The pharmacokinetics of three routes of administration of 5-Fluorouracil intraperitoneal, intravenous and intragastric chemotherapy in rabbits were comparatively studied by high performance liquid chromatography. RESULTS: High-dose intraperitoneal administration of high-dose drug in the abdominal cavity, portal vein and liver provided long-term maintenance and the elimination half-life (T ½ (1/2)) of peritoneal fluid and portal vein were 3.81 ± 0.14 h and 1.28 ± 0.09 h, while the peripheral blood drug concentration was very low. The peak concentrations of peritoneal fluid and portal vein drug were 206 times and 6.7 times that of the femoral vein, respectively. The peripheral plasma concentration and portal vein plasma concentration were higher in intravenous administration, but the effective plasma concentration maintenance time was shorter. The T 1/2 (1/2) β was 0.71 ± 0.02 h and 0.67 ± 0.04 h, respectively. After intragastric administration, the concentration of peritoneal liquid medicine is very low. Although the blood concentration of portal vein is higher than that of peripheral blood, the absorption is extremely irregular and the individual difference is larger. Tissue Chinese medicine concentration test 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. CONCLUSIONS: These pharmacokinetic characteristics suggest that intraperitoneal recurrence and liver metastases in patients with postoperative gastrointestinal malignancy are better than those with conventional intravenous chemotherapy and oral administration. Is an ideal postoperative adjuvant chemotherapy, can be used as a routine measure for gastrointestinal cancer postoperative chemotherapy.