Zhou X J, Placidi M, Rahmani R
Institut National de la Santé et de la Recherche Médicale, Centre INRA, Antibes, France.
Anticancer Res. 1994 May-Jun;14(3A):1017-22.
A study was carried out to evaluate the uptake, release and metabolism of four currently used vinca alkaloids, including vinblastine, vincristine, vindesine and navelbine, using freshly isolated human hepatocytes in suspension. The drugs were rapidly taken up and intensely metabolised by the cells, giving a number of yet unidentified biotransformation products. Navelbine was the most rapidly and intensely accumulated drug followed by vinblastine, vindesine and vincristine. The extent of cell uptake appeared to parallel the lipophilicities of these compounds. Interestingly, we found a significant correlation between the mean uptake rates of the vinca alkaloids into the cells, which were 0.279, 0.343, 0.568 and 0.834 pmol/min/10(6) cells for vincristine, vindesine, vinblastine and navelbine, respectively, and the in vivo plasma clearances of the drugs (r = 0.9995, p < 0.001). This finding is of great importance as regards a better understanding of the structure-activity relationship among this class of antitumour drugs, as well as a reliable extrapolation of in vitro results to the in vivo situation.
利用新鲜分离的悬浮人肝细胞开展了一项研究，以评估四种目前使用的长春花生物碱（包括长春碱、长春新碱、长春地辛和诺维本）的摄取、释放和代谢情况。这些药物被细胞快速摄取并强烈代谢，产生了一些尚未鉴定的生物转化产物。诺维本是积累最快且最强烈的药物，其次是长春碱、长春地辛和长春新碱。细胞摄取程度似乎与这些化合物的亲脂性平行。有趣的是，我们发现长春花生物碱进入细胞的平均摄取速率（长春新碱、长春地辛、长春碱和诺维本分别为0.279、0.343、0.568和0.834 pmol/分钟/10⁶个细胞）与药物的体内血浆清除率之间存在显著相关性（r = 0.9995，p < 0.001）。这一发现对于更好地理解这类抗肿瘤药物的构效关系以及将体外结果可靠地外推至体内情况具有重要意义。
