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Pharmacokinetic of Arsenic Trioxide in Newly Diagnosed Acute Promyelocytic Leukemia Patients

Keywords: Arsenic trioxide , pharmacokinetic , newly diagnosed APL , Graphite furnace atomic absorption

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Abstract:

The high complete remission rate with arsenic trioxide (ATO) in relapsed Acute Promyelocytic Leukemia (APL) patients has been led to its use in newly diagnosed patients. Twenty newly diagnosed APL patients between January 2006 and 2007 received 2 h intravenous infusion of 10 mg day-1 arsenic trioxide for induction therapy until achieving complete remission. Plasma arsenic concentration was analyzed by graphite furnace atomic absorption method by dilution of plasma with a suitable matrix modifier. The concentration of arsenic in 24 h urine of patients was measured by using a valid standard addition method and a suitable matrix modifier. The Limits of Detection (LOD) were 1.2 and 1.5 μg L-1 for arsenic in plasma and urine, respectively. Pharmacokinetic parameters of 20 patients were as following: Cmax: 43.6 ±19.5 μg L-1, tmax: 2.15±0.7 h, AUC0-24: 683±317 μg h L-1, AUC0-∞: 2027±958 μg h L-1, t1/2: 41±10 h, kel: 0.02±0.01 h-1, Vd: 5.6±3.6 L kg-1 and Cltotal: 0.1±0.05 L kg-1 h-1. During the first day of induction, 1.4±0.2% of administrated arsenic excreted into urine. Renal clearance was 5.1±4.1 mL kg-1 h-1. However, the results showed that the pharmacokinetic of ATO in newly diagnosed APL patients weren`t dependent to the sex of patients.

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