[A clinical pharmacokinetic study of multi-dose oral tetra-arsenic tetra-sulfide combination therapy in acute promyelocytic leukemia]

Abstract

Objective: To study the pharmacokinetics of multi-dose oral tetra-arsenic tetra-sulfide (As(4)S(4)) in acute promyelocytic leukemia (APL) patients and its major side effects.

Methods: Clinical pharmacokinetic study of As(4)S(4) was carried out in 7 patients who had never used arsenic before. The total concentration of arsenic in blood, urine and hair was determined with hydride generation-atomic absorption spectrometry.

Results: These patients were administrated oral As(4)S(4) complex capsule 20 mg/kg three times a day for 14 days. From day 10 and to day 14, the blood arsenic concentration and urinary arsenic excretion reached a steady state. The average minimal concentration (Cmin) and maximal concentration (Cmax) of blood arsenic was (53.3 +/- 9.0) microg/L and (70.7 +/- 10.8) microg/L. t 1/2 was prolonged to (70.7 +/- 31.7) hour, and area under curve (AUC) was (448.9 +/- 71.8) microg. h(-1).L(-1). Median time to peak concentration (Tmax) was 1 (range 0.5 - 8) hour. During As(4)S(4) therapy, 24-hour arsenic content in urine was (6170.8 +/- 3141.8) microg/L and it accounted for about (0.152 +/- 0.082)% of the total daily dosage. It decreased steadily over time after drug withdrawal, arsenic accumulated in hair and the concentration could be ten-fold higher than that before treatment.

Conclusion: Multi-dose oral As(4)S(4) is safe and has been relatively well tolerated in APL patients in spite of the tendency of its retention in some tissues after long time administration.