Pharmacokinetics of intravenous arsenic trioxide in the treatment of acute promyelocytic leukemia.
OBJECTIVE
To study the pharmacokinetics and metabolism of arsenic trioixide (As2O3) and its main side effects.


METHODS
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.


CONCLUSIONS
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.
Department of Immunogenetics, Shanghai Institute of Transfusion, Shanghai Blood Centre, Shanghai, 200051, China.
J
J
Ni
G
G
Chen
Z
Z
Shen
X
X
Li
H
H
Liu
Y
Y
Huang
Z
Z
Fang
S
S
Chen
Z
Z
Wang
Z
Z
Chen
D000293:Adolescent; D000328:Adult; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012008:Recurrence
D001152:Arsenicals; D010087:Oxides; D000077237:Arsenic Trioxide