Ooi K, Ohkubo T, Kuwabara H, Higashigawa M, Sakurai M
Department of Pharmacy, Social Insurance Hazu Hospital, Yokkaichi, Japan.
Yakugaku Zasshi. 1992 Nov;112(11):832-6. doi: 10.1248/yakushi1947.112.11_832.
We studied the effects of etoposide on the influx, intracellular accumulation and efflux of ara-C in P388 leukemic cells. Etoposide inhibited the active influx of ara-C in a dose dependent manner, and the inhibition was reversible. Etoposide also affected the intracellular accumulation of ara-C, though its inhibitory effect for the intracellular accumulation was weaker than that for the influx of ara-C. It was also shown that etoposide inhibited the active efflux of ara-C. Furthermore, etoposide inhibited the active transport of ara-C bidirectionally but the insensitive route of etoposide existed especially at high concentration of ara-C. The effect of inhibition of the transport of ara-C on the accumulation of ara-C was more significant at lower concentration of ara-C. Judging from the drug concentrations used in this study, an interaction between etoposide and ara-C could occur in the clinical treatment.
我们研究了依托泊苷对P388白血病细胞中阿糖胞苷的流入、细胞内蓄积及流出的影响。依托泊苷以剂量依赖性方式抑制阿糖胞苷的主动流入,且这种抑制是可逆的。依托泊苷也影响阿糖胞苷的细胞内蓄积,尽管其对细胞内蓄积的抑制作用比对阿糖胞苷流入的抑制作用弱。还表明依托泊苷抑制阿糖胞苷的主动流出。此外,依托泊苷双向抑制阿糖胞苷的主动转运,但在阿糖胞苷高浓度时尤其存在对依托泊苷不敏感的途径。在阿糖胞苷较低浓度时,抑制阿糖胞苷转运对其蓄积的影响更为显著。从本研究中使用的药物浓度判断,在临床治疗中依托泊苷与阿糖胞苷之间可能会发生相互作用。