静脉注射三氧化二砷治疗急性早幼粒细胞白血病的药代动力学

Pharmacokinetics of intravenous arsenic trioxide in the treatment of acute promyelocytic leukemia.

作者信息

Ni J, Chen G, Shen Z, Li X, Liu H, Huang Y, Fang Z, Chen S, Wang Z, Chen Z

机构信息

Department of Immunogenetics, Shanghai Institute of Transfusion, Shanghai Blood Centre, Shanghai, 200051, China.

出版信息

Chin Med J (Engl). 1998 Dec;111(12):1107-10.

PMID:11263375

Abstract

OBJECTIVE

To study the pharmacokinetics and metabolism of arsenic trioixide (As2O3) and its main side effects.

METHOD

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.

RESULTS

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.

CONCLUSION

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.

摘要

目的

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。

方法

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。

结果

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。