Nilsson S O, Andersson B, Eksborg S, Beran M, Ehrsson H
Cancer Chemother Pharmacol. 1981;5(4):261-6. doi: 10.1007/BF00434395.
An earlier whole-body autoradiographic study in mice revealed large differences between the tissue distribution of daunorubicin (D) after administration as free drug as as DNA-linked D. Therefore, the pharmacokinetics of D administered as free drug or linked to DNA was studied in 15 adult patients with acute non-lymphoblastic leukemia. The data obtained following infusion of free drug over either 45 or 240 min could be fitted to a two-compartment open-body model. With the D-DNA infusion considerably higher plasma concentrations were achieved, with a slower distribution and elimination from plasma than seen after the administration of free drug. this confirmed earlier animal data indicating a different pharmacokinetic behavior of D when it was administered linked to DNA. Furthermore, different pharmacokinetic parameters were obtained for D during infusion and in the post-infusion phase after administration of DNA-linked D (P less than 0.005). This finding strongly indicates that the D-DNA acts as a slow-release preparation in humans, which might modify tissue distribution and toxic side-effects of the drug.
一项早期针对小鼠的全身放射自显影研究显示，柔红霉素（D）作为游离药物给药与作为DNA结合型D给药后的组织分布存在巨大差异。因此，在15例急性非淋巴细胞白血病成年患者中研究了游离药物形式或与DNA结合形式的D的药代动力学。在45分钟或240分钟内输注游离药物后获得的数据可拟合为二室开放体模型。通过输注D-DNA可实现显著更高的血浆浓度，与游离药物给药后相比，其在血浆中的分布和消除更慢。这证实了早期的动物数据，表明与DNA结合给药时D具有不同的药代动力学行为。此外，在输注DNA结合型D期间及输注后阶段，D获得了不同的药代动力学参数（P<0.005）。这一发现有力地表明，D-DNA在人体内起到缓释制剂的作用，这可能会改变药物的组织分布和毒副作用。
