进展期胃癌术前顺铂腹腔内、静脉化疗药代动力学的比较研究

Study on cisplatin pharmacokinetics:preoperative intraperitoneal administration versus intravenous chemotherapy with cisplatin for advanced gastric carcinoma

目的:比较研究进展期胃癌术前顺铂静脉与腹腔内给药的药代动力学特点。方法:50例可切除进展期胃癌患者随机分成两组:腹腔给药组26例,静脉给药组24例。顺铂60 mg/m2分别于术前腹腔及静脉给药,给药后180 min,取腹腔液、胃左静脉血、外周血标本;270 min取手术中肿瘤组织、癌旁正常组织标本。另取8例分两组分别作顺铂腹腔内给药与静脉给药的药代动力学研究。测定各组织的铂含量作为顺铂的浓度指标,铂浓度采用石墨炉原子分光光谱分析法测定。结果:顺铂腹腔给药时,在腹腔内可维持较长时间的高浓度,而血浆内的药物浓度与静脉给药时相近;腹腔给药时AUC为静脉给药时的近5倍;顺铂术前给药后,腹腔给药组腹腔液、胃左静脉的总铂浓度明显高于静脉给药组(P<0.01),分别高于静脉给药组的23.4倍、2.53倍;肿瘤组织内的浓度也比静脉给药组高,差异有统计学意义(P<0.05)。结论:顺铂腹腔内给药具有明显的药代动力学优势,可作为进展期胃癌有效的辅助治疗手段。

AIM： To compare the characteristics of cisplatin pharmacokinetics： preoperative intraperitoneal administration versus intravenous chemotherapy with cisplatin for advanced gastric carcinoma. METHODS： 50 patients with resectable advanced gastric cancer were randomly divided into 2 groups： 26 cases with preoperative intraperitoneal administration of cisplatin （ i. p. group） and 24 cases with preoperative intravenous administration of cisplatin （ i.v. group）. Each patient was given 60 mg/m^2 cisplatin intraperitoneally or intravenously. The peritoneal fluid, blood from gastric sinistral vein and peripheral blood were taken on the 180th minutes after the drug was administrated. Cancer tissues and normal tissues beside the cancer tissue were collected at the 270th minutes during operation. Another 8 cases were used to study the pharmacokinetics of intraperitoneal administration and intravenous chemotherapy with cisplatin. The concentrations of cisplatin in different samples were measured by the flameless type of atomic absorption spectrometry. RESULTS：The high cisplatin concentration in abdominal cavity could maintain for fairly longer time by intraperitoneal administration more than by intravenous administration. And the plasma concentrations of cisplatin in peritoneal cavity were similar by the two injection styles. The AUC with intraperitoneal administration was about five times than that with intravenous administration. The cisplatin concentrations of peritoneal fluid and vena gastrica sinistra blood in the i.p. group were 23.4 and 2.53 times higher than those in the i.v. group respectively （ P 〈 0.01 ）. The cisplatin of the cancer tissue in the i.p. group was higher than that in the i. v. group（ P 〈 0.05）. CONCLUSION： The intraperitioheal cisplatin chemotherapy has better pharmacokinetics parameters and could be a useful accessory treatment for the advanced gastric carcinoma cancer.