Clinical Pharmacokinetic Study of Arsenic Trioxide in an Acute Promyelocytic Leukemia (APL) Patient: Speciation of Arsenic Metabolites in Serum and Urine

Abstract

The pharmacokinetics of arsenic species in a Japanese patient with relapsed acute promyelocytic leukemia (APL) treated with arsenic trioxide at a daily dose of 0.08 mg/kg was investigated. After achieving complete remission on Day 35 during the induction therapy of arsenic trioxide, we collected the serum and urine samples on Days 4 and 5 during the consolidation therapy of arsenic trioxide. The concentrations of inorganic arsenic and the methylated metabolites in serum and urine were measured by HPLC/ICP-MS. The patient restricted taking the seafood for 3 d before the start of administration and during the sampling period in order to avoid the influence of arsenic derived from seafood. Arsenite (As^III), methylarsonic acid (MMAs^V), and dimethylarsinic acid (DMAs^V) were detected in serum and urine. The total concentration of As^III, MMAs^V and DMAs^V in serum ranged from 18 to 41 μg/l (240—547 nM) during 24 h on Day 4. The amount of total arsenic (As^III+MMAs^V+DMAs^V) in urine was 4464 μg/d on Day 4. These results suggest that not the micro-molar but the nano-molar order of arsenic in serum is sufficient to produce the therapeutic effect on APL cells.