[Pharmacokinetics of intravenous arsenic trioxide in the treatment of acute promyelocytic leukemia].
OBJECTIVE
In order to study the pharmacokinetics and metabolism of arsenic trioxide (As22O3), and its major side effects.


METHODS
The clinical pharmacokinetics of intravenous As2O3 in 8 relapsed acute promyelocytic leukemia (APL) patients were studied by Gas-phase chromotography.


RESULTS
(1) After 2 hour intravenous drips of 10mg As2O3, drug plasma maximal concentration (Cpmax) was 0.94 +/- 0.37mg/L(x +/- s), time to peak concentration (Tp) was 4hrs, T1/2 alpha and T1/2beta were 0.89 +/- 0.29hrs and 12.13 +/- 3.31hrs, respectively, apparent volume of distribution (Vc) was 3.83 +/- 0.45L, system clearance (CLs) was 1.43 +/- 0.17L/h and area under curve (AUC) was 7.25 +/- 0.97mg x h/L. Importantly, the continuous administration of As2O3 did not alter the pharmacokinetic behaviors. (2) During As2O3 therapy, 24-hour arsenic content in urine accounted for 1%-8% of the total dose (10mg) per day. And it decreased gradually after drug withdrawal. (3) Arsenic contents in nail and hair were increased continuously during As2O3 therapy. The peak concentrations could be five to seven-fold higher than that pre-treatment. It also decreased gradually after drug with drawal.


CONCLUSIONS
As2O3 is a relatively safe and effective drug in the treatment of APL patients, in spite of certain accumulation in some tissues.
Ni
J
J
Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025.
Chen
G
G
Shen
Z
Z
Li
X
X
Liu
H
H
Huang
Y
Y
Fang
Z
Z
Chen
S
S
Wang
Z
Z
Chen
L
L
D000293:Adolescent; D000328:Adult; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005260:Female; D006197:Hair / Q000378:metabolism; D006801:Humans; D007262:Infusions, Intravenous; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism* / Q000652:urine; D008297:Male; D008875:Middle Aged; D009262:Nails / Q000378:metabolism; D010087:Oxides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
D001152:Arsenicals; D010087:Oxides; D000077237:Arsenic Trioxide