Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Clinical Pharmacokinetic Study of Arsenic Trioxide in an Acute Promyelocytic Leukemia (APL) Patient: Speciation of Arsenic Metabolites in Serum and Urine
Yasuomi FukaiMiyuki HirataMayumi UenoNaoaki IchikawaHikaru KobayashiHiroshi SaitohTeruaki SakuraiKenji KinoshitaToshikazu KaiseShin Ohta
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2006 Volume 29 Issue 5 Pages 1022-1027

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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.

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© 2006 The Pharmaceutical Society of Japan
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