OBJECTIVE: To study the pharmacokinetics and metabolism of arsenic trioixide (As2O3) and its main side effects. METHOD: 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. CONCLUSION: 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.
OBJECTIVE: To study the pharmacokinetics and metabolism of arsenic trioixide (As2O3) and its main side effects. METHOD: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. CONCLUSION: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.
Authors: Haimei Chen; Richard Ahn; Jeroen Van den Bossche; David H Thompson; Thomas V O'Halloran Journal: Mol Cancer Ther Date: 2009-06-30 Impact factor: 6.261
Authors: Peter Westervelt; Jessica L Pollock; Kristie M Oldfather; Matthew J Walter; Margaret K Ma; Anthony Williams; John F DiPersio; Timothy J Ley Journal: Proc Natl Acad Sci U S A Date: 2002-06-20 Impact factor: 11.205