Clinical pharmacokinetic study of arsenic trioxide in an acute promyelocytic leukemia (APL) patient: Speciation of arsenic metabolites in serum and urine

Yasuomi Fukai, Miyuki Hirata, Mayumi Ueno, Naoaki Ichikawa, Hikaru Kobayashi, Hiroshi Saitoh, Teruaki Sakurai, Kenji Kinoshita, Toshikazu Kaise, Shin Ohta

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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 (AsIII), methylarsonic acid (MMAsV), and dimethylarsinic acid (DMAsV) were detected in serum and urine. The total concentration of AsIII, MMAsV and DMAsV in serum ranged from 18 to 41 μg/l (240-547 nM) during 24 h on Day 4. The amount of total arsenic (AsIII+MMAsV+DMAsV) 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.

Original languageEnglish
Pages (from-to)1022-1027
Number of pages6
JournalBiological and Pharmaceutical Bulletin
Volume29
Issue number5
DOIs
Publication statusPublished - May 2006

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

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