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


CONCLUSIONS
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.
Wang
Feng-rong
FR
The People's Hospital and Institute of Hematology, Peking University, Beijing 100044, China.
Lou
Ya-qing
YQ
Lu
Dao-pei
DP
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001151:Arsenic / Q000378:metabolism; D001152:Arsenicals / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D006197:Hair / Q000737:chemistry; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008297:Male; D013440:Sulfides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D000970:Antineoplastic Agents; D001152:Arsenicals; D013440:Sulfides; D001151:Arsenic