Pharmacokinetics of intravenous arsenic trioxide in the treatment of acute promyelocytic leukemia
Ni, J.; Chen, G.; Shen, Z.; Li, X.; Liu, H.; Huang, Y.; Fang, Z.; Chen, S.; Wang, Z.; Chen, Z.
Chinese Medical Journal 111(12): 1107-1110
1998
ISSN/ISBN: 0366-6999 PMID: 11263375 Document Number: 495084
To study the pharmacokinetics and metabolism of arsenic trioixide (As2O3) and its main side effects. 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. 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. 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.