Wang Y
Institute of Hepatobiliary Surgery, Second Miliary Medical University, Shanghai.
Zhonghua Wai Ke Za Zhi. 1990 Nov;28(11):686-8, 704.
After injection into the hepatic artery of New Zealand rabbits of microencapsulated CDDP (CDDPmc,group A) and non-encapsulated CDDP (group B), the platinum concentrations in sera and in the liver, lung, heart and renal tissues were determined and the hepatic and renal function monitored at various time intervals. The serum platinum concentration in group A increased slowly following administration of CDDPmc and gradually decreased after reaching its highest level. In contrast, it reached the maximum level immediately after the injection of CDDP and then decreased rapidly in group B, with the peak concentration being 4.5 times as high as that in group A. The hepatic tissues maintained a high level of the platinum for at least 21 days after the injection in group A, but for only a short period of time in group B. The platinum level was found to be low in the lung and heart tissues and high in the renal tissues in both groups, with the renal concentration being much higher in group B than in group A. The animals of both groups suffered some extent of hepatic and renal disfunction, but again, it was much more severe for animals in group B. The above results demonstrated that drug concentration in target tissues could be kept at a higher level, and in circulating blood at a lower level by the microcapsule technique than by the conventional administration technique, raising hopes that the therapeutic effect might be enhanced and the general side effects of CDDP reduced.
将微囊化顺铂(CDDPmc,A组)和未微囊化顺铂(B组)注入新西兰兔肝动脉后,测定不同时间间隔血清、肝、肺、心和肾组织中的铂浓度,并监测肝肾功能。A组给予CDDPmc后血清铂浓度缓慢升高,达到最高水平后逐渐下降。相比之下,B组注射CDDP后立即达到最高水平,然后迅速下降,峰值浓度是A组的4.5倍。A组注射后肝组织中铂水平至少维持21天,而B组仅维持短时间。两组肺和心组织中铂水平较低,肾组织中铂水平较高,B组肾组织中的浓度远高于A组。两组动物均出现一定程度的肝肾功能障碍,但B组动物的情况更为严重。上述结果表明,与传统给药技术相比,微囊技术可使靶组织中的药物浓度保持在较高水平,循环血液中的药物浓度保持在较低水平,有望提高顺铂的治疗效果并降低其总体副作用。