Speth P A, van de Loo F A, Linssen P C, Wessels H M, Haanen C
Clin Pharmacol Ther. 1986 Dec;40(6):643-9. doi: 10.1038/clpt.1986.239.
On 3 consecutive days, 4-demethoxydaunomycin (D-DNM) was administered orally (30 mg/m2) as bolus injection and 4- or 24-hour infusion to seven patients with acute leukemia. Cellular (nucleated blood and bone marrow cells) and plasma drug concentrations were studied. After bolus injection, peak plasma D-DNM concentrations were about 50 mg/ml. D-DNM plasma t1/2s were 0.4 +/- 0.3 hours (T1/2 alpha) and 16.4 +/- 4.7 hours (T1/2 beta). D-DNM concentrations in nucleated blood and bone marrow cells were on the same order of magnitude and amounted to more than 400 times the plasma concentration, whereas 4-demethoxydaunomycinol (D-DNMol) concentrations were about 200 times higher. Cellular D-DNM concentrations were maximal at the end of intravenous dosing and at 2 to 4 hours after D-DNM ingestion. D-DNMol concentrations increased more slowly and accumulated on subsequent treatment days in cells and plasma; D-DNM and D-DNMol cellular t1/2 times were 42 and 72 hours, respectively. Antileukemic activity was observed.
连续3天，对7例急性白血病患者口服给予4-去甲氧基柔红霉素（D-DNM）（30mg/m²），采用静脉推注及4小时或24小时输注的方式。研究了细胞（有核血细胞和骨髓细胞）及血浆中的药物浓度。静脉推注后，血浆D-DNM的峰值浓度约为50mg/ml。D-DNM的血浆半衰期分别为0.4±0.3小时（T1/2α）和16.4±4.7小时（T1/2β）。有核血细胞和骨髓细胞中的D-DNM浓度处于同一数量级，且高于血浆浓度400多倍，而4-去甲氧基柔红霉醇（D-DNMol）的浓度则高出约200倍。细胞内D-DNM浓度在静脉给药结束时及摄入D-DNM后2至4小时达到最大值。D-DNMol浓度上升较为缓慢，并在后续治疗日在细胞和血浆中蓄积；细胞内D-DNM和D-DNMol的半衰期分别为42小时和72小时。观察到了抗白血病活性。
