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

doi:10.1248/bpb.29.1022

Notes

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

Author information

Yasuomi Fukai
Department of Pharmacy, Nagano Red Cross Hospital
Miyuki Hirata
Hygiene, Graduate School of Medical Sciences, Kyushu University
Mayumi Ueno
First-Internal Medicine, Nagano Red Cross Hospital
Naoaki Ichikawa
First-Internal Medicine, Nagano Red Cross Hospital
Hikaru Kobayashi
First-Internal Medicine, Nagano Red Cross Hospital
Hiroshi Saitoh
First-Internal Medicine, Nagano Red Cross Hospital
Teruaki Sakurai
Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University
Kenji Kinoshita
Laboratory of Environmental Chemodynamics, School of Life Science, Tokyo University of Pharmacy and Life Science
Toshikazu Kaise
Laboratory of Environmental Chemodynamics, School of Life Science, Tokyo University of Pharmacy and Life Science
Shin Ohta
Department of Pharmacy, Nagano Red Cross Hospital

Keywords: acute promyelocytic leukemia (APL), arsenic trioxide, arsenic metabolite, serum concentration, urinary excretion

JOURNAL FREE ACCESS

2006 Volume 29 Issue 5 Pages 1022-1027

DOI https://doi.org/10.1248/bpb.29.1022

Details

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.

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