Pharmacology and antitumour effects of intraportal pirarubicin on experimental liver metastases.
Pharmacology and antitumour effects of intraportal pirarubicin on experimental liver metastases.
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DOI：
10.1038/bjc.1993.328
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发表时间：
1993-08
影响因子：
8.8
通讯作者：
Rougier, P
中科院分区：
文献类型：
--
作者：
Ramirez, L H;Munck, J N;Bognel, C;Zhao, Z;Ardouin, P;Poupon, M F;Gouyette, A;Rougier, P
早期肝转移主要由门静脉供血。门静脉内（i.port.）理论上，静脉给予细胞毒素可以提高肿瘤细胞中的药物浓度，并在结肠直肠癌切除术后作为辅助治疗有效。在VX 2兔肿瘤的肝转移上研究了吡拉韦（其具有比多柔比星更高的肝提取），所述VX 2兔肿瘤在细胞注射到门静脉中后7天直径小于2 mm。为了评价抗肿瘤活性，在植入后7天，将24只家兔随机分为三组：（a）对照组，（B）静脉注射吡拉西坦组，（c）静脉注射吡拉西坦组。在两组中，吡拉罗肽的剂量为2 mg kg-1。门静脉输注未导致血液学或肝脏毒性。药代动力学参数显示，i. port后全身暴露量显著降低。局治疗后14天，分析肝脏和肺。平均数（+/- s.d.）肿瘤灶的平均直径为（a）8.62（± 5.4），（B）4.62（± 3.2），（c）2.25（± 1.4）（P < 0.05 a vs c）。平均肿瘤面积为（a）6.31（+/- 6.1），（B）1.31（+/- 2.2），（c）0.43（+/- 0.4 cm 2）（P < 0.05 a vs c），百分比（95% C.I.）兔肺转移瘤的发生率为：（a）87.5%（47-99%），（B）75%（35-97%），（c）12.5%（3-52%）（P <B c）。门静脉内吡拉齐似乎耐受性良好，比静脉给药更有效，特别是在预防肝外播散方面。
Early liver metastases have a predominant portal blood supply. Intraportal (i.port.) vein administration of cytotoxics could theoretically achieve enhanced drug concentrations in tumour cells and be effective as adjuvant therapy after resection of colorectal carcinoma. Pirarubicin (which has a higher hepatic extraction than doxorubicin) was investigated on liver metastases of the VX2 rabbit tumour, which were of less than 2 mm in diameter 7 days after cells injection into the portal vein. To evaluate antitumour activity, 24 rabbits were randomised into three groups 7 days after implantation: (a) control, (b) i.v. pirarubicin, (c) i.port. pirarubicin at doses of 2 mg kg-1 in both groups. Portal infusions led to no hematological or hepatic toxicity. Pharmacokinetic parameters showed a significantly reduced systemic exposure after i.port. administration. Fourteen days after treatment, livers and lungs were analysed. The mean number (+/- s.d.) of tumour foci was (a) 8.62 (+/- 5.4), (b) 4.62 (+/- 3.2), (c) 2.25 (+/- 1.4) (P < 0.05 a vs c). The mean tumour area was (a) 6.31 (+/- 6.1), (b) 1.31 (+/- 2.2), (c) 0.43 (+/- 0.4 cm2) (P < 0.05 a vs c) and the percentage (95% C.I.) of rabbits with lung metastasis was: (a) 87.5% (47-99%), (b) 75% (35-97%), (c) 12.5% (3-52%) (P < 0.02 b vs c). Intraportal pirarubicin seems to be well tolerated and more efficient than i.v. administration, particularly in preventing extrahepatic dissemination.