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

概要

論文の詳細を見る
The pharmacokinetics of arsenic species in a Japanese patient with relapsed acute promyelocytic leukemia (APL) treated with arsenic trioxide at a daily dose of 0.08mg/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 dimethyl-arsinic 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 41μg/l (240-547 nM) during 24 h on Day 4. The amount of total arsenic (As^<III>+MMAs^v+DMAs^v) in urine was 4464μg/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.
2006-05-01