Kar R, Opfell R W, Wile A G
Department of Surgery, University of California, Irvine.
Cancer Drug Deliv. 1987;4(4):225-32. doi: 10.1089/cdd.1987.4.225.
The pharmacology of hepatic regional administration of CisplatinR (DDP) was examined in a rabbit model. Routes and modes of administration were: IV, hepatic arterial infusion (HAI), HAI with stopflow, HAI with microembolic material [collagen for embolization (CFE)], and portal vein (PV). DDP was rapidly administered, blood samples were drawn over 45 minutes, and hepatic tissue was obtained. Filterable plasma DDP levels were measured by HPLC. Hepatic DDP levels were determined by atomic absorption spectroscopy. All modes of regional administration yielded significantly higher hepatic DDP levels when compared to tissue levels following IV administration. Only the PV and HACFE routes resulted in significantly less systemic drug exposure (AUC) when compared to IV administration. These data indicate a relative pharmacologic advantage of 1.8 for HAI, 3.4 for PV, 1.8 for HAI stopflow, and 4.3 for HACFE compared to IV DDP administration. This pre-clinical study demonstrates substantial pharmacologic advantage for PV and HACFE routes of DDP administration and suggests that clinical trials based on this information be considered.
在兔模型中研究了顺铂（DDP）肝区给药的药理学。给药途径和方式包括：静脉注射（IV）、肝动脉灌注（HAI）、阻断血流的肝动脉灌注（HAI with stopflow）、含微栓塞材料的肝动脉灌注[用于栓塞的胶原蛋白（CFE）]以及门静脉（PV）。快速给予DDP，在45分钟内采集血样，并获取肝组织。通过高效液相色谱法（HPLC）测定可滤过血浆DDP水平。通过原子吸收光谱法测定肝DDP水平。与静脉注射后组织水平相比，所有区域给药方式产生的肝DDP水平均显著更高。与静脉注射相比，仅PV和HACFE途径导致全身药物暴露（AUC）显著减少。这些数据表明，与静脉注射DDP相比，HAI的相对药理学优势为1.8，PV为3.4，HAI stopflow为1.8，HACFE为4.3。这项临床前研究证明了PV和HACFE途径给予DDP具有显著的药理学优势，并建议考虑基于该信息进行临床试验。
