title: Clinical pharmacokinetic study of arsenic trioxide in an acute promyelocytic leukemia (APL) patient: speciation of arsenic metabolites in serum and urine.
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 microg/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 microg/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.
authors.affiliation: Department of Pharmacy, Nagano Red Cross Hospital, Nagano, Japan. y-fukai@nagano-med.jrc.or.jp
authors.forename: Yasuomi
authors.initials: Y
authors.lastname: Fukai
authors.forename: Miyuki
authors.initials: M
authors.lastname: Hirata
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ueno
authors.forename: Naoaki
authors.initials: N
authors.lastname: Ichikawa
authors.forename: Hikaru
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saitoh
authors.forename: Teruaki
authors.initials: T
authors.lastname: Sakurai
authors.forename: Kenji
authors.initials: K
authors.lastname: Kinoshita
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Kaise
authors.forename: Shin
authors.initials: S
authors.lastname: Ohta
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000009:adverse effects / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007275:Injections, Intravenous; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism*; D008297:Male; D008745:Methylation; D010087:Oxides / Q000009:adverse effects / Q000493:pharmacokinetics*; D017747:Seafood / Q000032:analysis; D014212:Tretinoin / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D014212:Tretinoin; D000077237:Arsenic Trioxide