Ni J, Chen G, Shen Z, Li X, Liu H, Huang Y, Fang Z, Chen S, Wang Z, Chen Z
Department of Immunogenetics, Shanghai Institute of Transfusion, Shanghai Blood Centre, Shanghai, 200051, China.
Chin Med J (Engl). 1998 Dec;111(12):1107-10.
To study the pharmacokinetics and metabolism of arsenic trioixide (As2O3) and its main side effects.
As2O3 was administered intravenously at the dose of 10 mg per day for the treatment of 8 relapsed acute promyelocytic leukemia (APL) patients. The arsenic content was measured by Gas-phase chromatography.
The plasma maximal concentration (Cpmax) was 0.94 +/- 0.37 mg/L (x +/- s), time to peak concentration (Tp) was 4 hours, plasma distribution half-time (t1/2 alpha) and elimination half-time (t1/2 beta) were 0.89 +/- 0.29 hours and 12.13 +/- 3.31 hours, respectively. Apparent distribution volume (Vc) was 3.83 +/- 0.45 L, system clearance (CLs) was 1.43 +/- 0.17 L/h, and area under curve (AUC) was 7.25 +/- 0.97 mg.h/L. The continuous administration of As2O3 did not alter its pharmacokinetic behaviors. During As2O3 treatment, 24-hour arsenic content in urine accounted for 1%-8% of the daily dose (10 mg). When arsenic accumulation in hair and nail increased continuously, the peak concentration could be five to seven-fold higher than that of pre-treatment. Importantly, arsenic contents in both urine and hair or nail declined gradually after drug withdrawal. No bone marrow suppression or severe organ-impairment was found.
As2O3 is a relatively safe and effective remedy in the treatment of patients with relapsed APL, in spite of certain degree of arsenic accumulation in some tissues.
研究三氧化二砷（As2O3）的药代动力学、代谢情况及其主要副作用。
对8例复发的急性早幼粒细胞白血病（APL）患者采用每日10 mg剂量静脉注射As2O3进行治疗。采用气相色谱法测定砷含量。
血浆最大浓度（Cpmax）为0.94±0.37 mg/L（x±s），达峰时间（Tp）为4小时，血浆分布半衰期（t1/2α）和消除半衰期（t1/2β）分别为0.89±0.29小时和12.13±3.31小时。表观分布容积（Vc）为3.83±0.45 L，系统清除率（CLs）为1.43±0.17 L/h，曲线下面积（AUC）为7.25±0.97 mg·h/L。连续给药As2O3未改变其药代动力学行为。As2O3治疗期间，24小时尿砷含量占日剂量（10 mg）的1% - 8%。当头发和指甲中的砷蓄积持续增加时，峰值浓度可比治疗前高5至7倍。重要的是，停药后尿砷及头发或指甲中的砷含量均逐渐下降。未发现骨髓抑制或严重器官损害。
尽管As2O3在某些组织中有一定程度的砷蓄积，但它是治疗复发APL患者相对安全有效的药物。
