顺铂腹腔热灌注化疗的药代动力学实验研究

Experimental Pharmacokinetic Study of Chemotherapeutic Hyperther-mic Intraperitoneal Perfusion (CHIP) with Cisplatin

目的 :探讨顺铂 (DDP)腹腔热灌注化疗 (CHIP)的药代动力学特点。方法 :家兔 1 5只 ,平均分为 3组。组 A(CHIP组 )用 DDP2 0 0 mg/ m2 溶于 41～ 42℃生理盐水 1 0 0 0 ml,腹腔循环灌注6 0 min。组 B(腹腔化疗组 )用 DDP90 mg/ m2 溶于 41～ 42℃生理盐水 2 0 0 ml,一次性腹腔注入。组 C(静脉用药组 )用 DDP90 mg/ m2静脉注射。液相色谱分析 2 4h内腹腔液和血浆 DDP浓度变化。结果 :组 A之腹腔液 DDP峰值浓度和 AUC(药时曲线下面积 )分别为血浆峰值和 AUC之 1 0倍和2 .9倍。组 A与组 C相比 ,腹腔液峰值和 AUC分别为 1 0 .4倍和 7.8倍 ,差异均有高度显著性意义(P<0 .0 0 1 ) ,血浆峰值较低 (P<0 .0 5)而 AUC较高 (P>0 .0 5)。组 A与组 B比较 ,后者腹腔液峰值更高 (P<0 .0 5) ,但 AUC较低 (P>0 .0 5)。结论 :CHIP腹腔 DDP浓度高 ,血浆峰值较低 ,以及高温作用 ,有利于化疗药物在局部对肿瘤细胞发挥作用 。

Objective: To observe the pharmcokinetics of chemotherapeutic hyperthermic intraperitoneal perfusion (CHIP) with cisplatin.Methods: Fifteen rabbits were divided into 3 groups. Group A (CHIP):Intraperitoneal perfusion with DDP 200mg/m 2,dissolved in 41～42℃ saline 1 000ml,persisted 60 min. Group B (IP):Intraperitoneal administration with DDP 90mg/m 2 dissolved in 41℃ saline 200ml. Group C (IV):DDP 90mg/m 2 dissolved in saline 100ml intravenous infusion during 60 min. DDP levels in plasma and peritoneal fluid during 24h were measured by high performance liquid chromatography. Results: In Group A,the peak concentration and peak area (AUC) of DDP in peritoneal fluid were 10 times and 2.9 times respectively higher than those in plasma. The peak concentration and peak area (AUC) of DDP in peritoneal fluid of group A were significantly higher than those of group C (P< 0.001 ),whereas the peak concentration and AUC in plasma of group A were lower (P= 0.038 and P= 0.309 ,respectively). Comparing group A with group B,the DDP peak concentration in peritoneal cavity of group B was higher (P=0.017) but AUC was lower (P= 0.49 ). Conclusion: CHIP provides high concentration of DDP in the peritoneal cavity,inducing higher local tumoricidal effect,lower nephric and systemic toxicity.