Burns C P, Haugstad B N, North J A
Biochem Pharmacol. 1987 Mar 15;36(6):857-60. doi: 10.1016/0006-2952(87)90176-6.
Transport of radiolabeled mitoxantrone, a new antineoplastic agent, was studied using cultured mouse L1210 leukemia cells. The initial velocity of influx remained linear for about 90 sec and was 110 pmoles/10(6) cells measured at 60 sec. The steady-state accumulation of about 480 pmoles/10(6) cells was not reached until 30 min. The unidirectional drug influx was linear from 0 to 1000 microM extracellular drug concentration. The initial uptake was relatively temperature independent between 37 degrees and 27 degrees, but accumulation at steady state was 17% lower at 27 degrees. None of six metabolic inhibitors had an appreciable effect on initial uptake. Efflux was initially exponential with a half-life of 2.8 min; this efflux and the residual drug concentration plateau were not affected by KCN or verapamil. Under steady-state conditions, about 86% of the cell-associated label was contained in parent drug and the remainder in an unidentified metabolite. These studies indicate that the mechanism of mitoxantrone uptake is passive diffusion. The efflux is not energy requiring, but there is considerable tight binding of the drug to cellular structures.
利用培养的小鼠L1210白血病细胞研究了新型抗肿瘤药物米托蒽醌的放射性标记物转运情况。内流的初始速度在约90秒内保持线性，在60秒时测得为110皮摩尔/10⁶个细胞。直到30分钟才达到约480皮摩尔/10⁶个细胞的稳态积累。从细胞外药物浓度0到1000微摩尔，单向药物内流呈线性。初始摄取在37℃和27℃之间相对不依赖温度，但在27℃时稳态积累降低17%。六种代谢抑制剂对初始摄取均无明显影响。外排最初呈指数形式，半衰期为2.8分钟；这种外排和残留药物浓度平台不受氰化钾或维拉帕米影响。在稳态条件下，约86%与细胞结合的标记物存在于母体药物中，其余存在于一种未鉴定的代谢物中。这些研究表明米托蒽醌摄取的机制是被动扩散。外排不需要能量，但药物与细胞结构有相当紧密的结合。
