Ku Y, Samizo M, Fukumoto T, Shiki H, Maekawa Y, Iwasaki T, Tominaga M, Kuroda Y, Saitoh Y
First Department of Surgery, Kobe University School of Medicine.
Nihon Shokakibyo Gakkai Zasshi. 1993 Jan;90(1):41-8.
Hepatic extraction rates (ER) of anticancer drugs during hepatic arterial infusion were investigated with the aid of direct hemoperfusion (DHP) under hepatic venous isolation (HVI). Using mongrel dogs (n = 6), adriamycin (ADR), mitomycin C (MMC) and cisplatin (CDDP) were simultaneously administered to the hepatic artery at each dosage of 1 mg/kg in 10 minutes under HVI.DHP. Hepatic venous flow and plasma concentrations of each drug at the carotid artery, the inlet and outlet sides of DHP were periodically determined during HVI.DHP. Based on these data, drug adsorption and removal rates were estimated. In addition, hepatic tissue uptakes of each drug were calculated from the amounts of drug administered and leaked in the hepatic effluent. Subsequently, the percentage of tissue uptake of each drug to the amount of drug administered was determined as ER of each drug. Drug adsorption rates during the first 10 minutes after infusion showed no significant difference among three drugs. Drug removal rate of CDDP tended to be higher than those of other two drugs. ER of CDDP (54.8 +/- 18.3%) were significantly lower (p < 0.01) as compared to ADR (84.4 +/- 16.2%) and MMC (83.1 +/- 15.7%). These results indicate that ER of each drug should be taken into consideration to determine appropriate drug for hepatic arterial chemotherapy.
在肝静脉隔离(HVI)下借助直接血液灌注(DHP)研究了肝动脉灌注抗癌药物时的肝提取率(ER)。使用杂种犬(n = 6),在HVI.DHP期间,阿霉素(ADR)、丝裂霉素C(MMC)和顺铂(CDDP)在10分钟内以1mg/kg的剂量同时注入肝动脉。在HVI.DHP期间定期测定肝静脉血流量以及每种药物在颈动脉、DHP进出口侧的血浆浓度。基于这些数据,估算药物吸附和清除率。此外,根据给药量和肝流出物中泄漏的药物量计算每种药物的肝组织摄取量。随后,将每种药物的组织摄取量占给药量的百分比确定为每种药物的ER。输注后最初10分钟内的药物吸附率在三种药物之间无显著差异。CDDP的药物清除率倾向于高于其他两种药物。与ADR(84.4±16.2%)和MMC(83.1±15.7%)相比,CDDP的ER(54.8±18.3%)显著较低(p < 0.01)。这些结果表明,在确定适合肝动脉化疗的药物时应考虑每种药物的ER。