Shiotani M, Ku Y, Kusunoki N, Kitagawa T, Maeda I, Tominaga M, Tanigawara Y, Kuroda Y, Saitoh Y
First Dept. of Surgery, Kobe University School of Medicine.
Gan To Kagaku Ryoho. 1995 Sep;22(11):1560-2.
We investigated the adriamycin (ADR) pharmacokinetics following intraarterial and intraportal infusion under hepatic venous isolation and charcoal hemoperfusion (HVI.CHP). HVI.CHP was used to measure the first-pass amount of adriamycin through the liver and to reduce hepatic re-entry of the drug. Beagles underwent a 10-min ADR infusion (1 mg/kg) either through the hepatic artery (group I, n = 5) or the portal vein (group II, n = 5) under a 20-min HVI.CHP. During HVI.CHP, the hepatic venous flow rate and plasma ADR levels in prefilter (hepatic venous level), postfilter and peripheral blood were serially measured. Based on these measurements, the hepatic extraction ratio (HER) of ADR was calculated. Areas under the time-concentration curves of prefilter levels in groups I and II were 6.1 +/- 1.6 and 16.9 +/- 5.0 micrograms.min/ml, respectively, showing a significant difference between two groups (p < 0.01). On the contrary, HER of group I (81.2%) was significantly higher than that of group II (47.2%, p < 0.01). These results indicate that intraarterial infusion of ADR is superior to intraportal infusion in terms of local drug delivery to the liver and systemic drug toxicities.
我们研究了在肝静脉隔离和活性炭血液灌注（HVI.CHP）下动脉内和门静脉内输注阿霉素（ADR）后的药代动力学。HVI.CHP用于测量阿霉素通过肝脏的首剂量，并减少药物的肝内再进入。在20分钟的HVI.CHP期间，比格犬通过肝动脉（I组，n = 5）或门静脉（II组，n = 5）接受10分钟的ADR输注（1 mg/kg）。在HVI.CHP期间，连续测量肝静脉流速以及过滤器前（肝静脉水平）、过滤器后和外周血中的血浆ADR水平。基于这些测量结果，计算ADR的肝提取率（HER）。I组和II组过滤器前水平的时间-浓度曲线下面积分别为6.1±1.6和16.9±5.0微克·分钟/毫升，两组之间存在显著差异（p < 0.01）。相反，I组的HER（81.2%）显著高于II组（47.2%，p < 0.01）。这些结果表明，就向肝脏的局部药物递送和全身药物毒性而言，动脉内输注ADR优于门静脉内输注。
