Kreis W, Chaudhri F, Chan K, Allen S, Budman D R, Schulman P, Weiselberg L, Freeman J, Deere M, Vinciguerra V
Cancer Res. 1985 Dec;45(12 Pt 1):6498-501.
The pharmacokinetic parameters of low dose 1-beta-D-arabinofuranosylcytosine (ara-C) infusions were studied in 11 patients, 6 males and 5 females, with a mean age of 68.5 +/- 13.8 (SD) years. The drug was infused to 4 patients with pre-leukemia (refractory anemia with excess blasts), 5 patients with acute myelogenous leukemia, and 2 patients with secondary leukemia due to chemotherapy, at a dosage of 20 mg/m2/day over 21 days. The patients' blood and urine were analyzed for ara-C content by radioimmunoassay. Mean steady state plasma levels of 7.7 +/- 4.7 ng/ml (31.7 +/- 19.3 nM) (n = 189) and a range 0.6 (2.5 nM) (lower limit of assay) to 29.7 ng/ml (122.1 nM), with significant inter- and intra-patient variations, were reached within about 2.7 h. The plasma levels of ara-C decreased rapidly, with a t1/2 alpha of about 12 min following discontinuation of the infusion, followed by a very slow t 1/2 beta of about 19 h. Other parameters (mean values of 10 or 11 patients) were: area under the curve, 182.1 +/- 64.8 ng X day/ml; total body clearance, 188.7 +/- 54.8 liters/h; renal clearance, 3.1 +/- 1.4 liters/h; volume of distribution at steady state, 53,913 +/- 17,626 liters; and recovery of ara-C in urine, 1.43 +/- 0.69% (n = 226) of daily administered ara-C. A linear relationship was observed with administered dose when the mean plasma levels of our study were compared with the ones reported for conventional ara-C infusions. Plasma clearance was comparable to that observed in conventional dose, when the observed values were extrapolated to the dose administered in this study.
对11例患者（6例男性，5例女性，平均年龄68.5±13.8（标准差）岁）进行了低剂量1-β-D-阿拉伯呋喃糖基胞嘧啶（阿糖胞苷）输注的药代动力学参数研究。将该药物以20mg/m²/天的剂量持续输注21天，分别给予4例患有白血病前期（原始细胞增多的难治性贫血）的患者、5例急性髓性白血病患者以及2例化疗所致继发性白血病患者。通过放射免疫分析法对患者的血液和尿液中的阿糖胞苷含量进行分析。约2.7小时内达到了平均稳态血浆水平7.7±4.7ng/ml（31.7±19.3nM）（n = 189），范围为0.6（2.5nM）（检测下限）至29.7ng/ml（122.1nM），患者间和患者内均存在显著差异。输注停止后，阿糖胞苷的血浆水平迅速下降，t1/2α约为12分钟，随后是非常缓慢的t1/2β约为19小时。其他参数（10或11例患者的平均值）为：曲线下面积，182.1±64.8ng·天/ml；总体清除率，188.7±54.8升/小时；肾清除率，3.1±1.4升/小时；稳态分布容积，53913±17626升；以及尿液中阿糖胞苷的回收率，为每日给药阿糖胞苷的1.43±0.69%（n = 226）。当将本研究的平均血浆水平与传统阿糖胞苷输注报道的水平进行比较时，观察到与给药剂量呈线性关系。当将观察值外推至本研究中给予的剂量时，血浆清除率与传统剂量下观察到的相当。
