title: Pharmacokinetics of arsenic species in Japanese patients with relapsed or refractory acute promyelocytic leukemia treated with arsenic trioxide.
abstract: OBJECTIVE
  To investigate the pharmacokinetics of arsenic species in Japanese patients with relapsed or refractory acute promyelocytic leukemia (APL) treated with arsenic trioxide (ATO) at a daily dose of 0.15 mg/kg.
  
  
  METHODS
  Inorganic arsenic (AsIII and AsV) and the major metabolites monomethylarsonic acid (MAA(V)) and dimethylarsinic acid (DMAA(V)) in plasma and urine collected from 12 Japanese patients were quantified by HPLC/ICP-MS.
  
  
  RESULTS
  The plasma concentrations of AsIII and AsV on day 1 reached the similar Cmax (12.4 +/- 8.4 and 10.2 +/- 3.9 ng/ml) immediately after completion of administration followed by a biphasic elimination. The AUC(0-infinity) of AsV was about twice that of AsIII. The appearance of methylated metabolites in the blood was delayed. During the repeated administration, the plasma concentrations of inorganic arsenic reached the steady state. In contrast, the MAA(V) and DMAA(V) concentrations increased in relation to increased administration frequency. The mean total arsenic excretion rate including inorganic arsenic and methylated arsenic was about 20% of daily dose on day 1 and remained at about 60% of daily dose during week 1-4.
  
  
  CONCLUSIONS
  This study demonstrates that ATO is metabolized when administered intravenously to APL patients and methylated metabolites are promptly eliminated from the blood and excreted into urine after completion of administration, indicating no measurable accumulation of ATO in the blood.
authors.affiliation: Department of Medicine III, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Fujisawa
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Ohno
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Shigeno
authors.forename: Naohi
authors.initials: N
authors.lastname: Sahara
authors.forename: Satoki
authors.initials: S
authors.lastname: Nakamura
authors.forename: Kensuke
authors.initials: K
authors.lastname: Naito
authors.forename: Miki
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Kaori
authors.initials: K
authors.lastname: Shinjo
authors.forename: Akihiro
authors.initials: A
authors.lastname: Takeshita
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Hisakuni
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Kinoshita
authors.forename: Masahito
authors.initials: M
authors.lastname: Shimoya
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Kaise
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ohnishi
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001151:Arsenic / Q000493:pharmacokinetics*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011446:Prospective Studies
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D001151:Arsenic; D000077237:Arsenic Trioxide