title: Speciation of arsenic trioxide penetrates into cerebrospinal fluid in patients with acute promyelocytic leukemia.
abstract: We assessed concentrations of arsenic trioxide (As(2)O(3)) and its metabolites in the plasma and cerebrospinal fluid in acute promyelocytic leukemia patients who achieved complete remission with intravenous As(2)O(3). Arsenic trioxide exists as high molecular mass proteins and low molecular mass proteins in the plasma, and metabolites seem to be able to penetrate blood-brain barrier. Methylarsonic acid (MA) in the cerebrospinal fluid is stably detected and its level was higher than that in plasma after As(2)O(3) treatment. Trivalent arsenic (AS(III)) and dimethylarsinic acid (DMA) became detectable after As(2)O(3) infusion, though the levels of arsenic metabolites in the cerebrospinal fluid was lower than plasma levels. Results suggest that a combinatory treatment of As(2)O(3) with other chemotherapeutics could be effective for APL patients with CNS involvement.
authors.affiliation: First Department of Internal Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. kiguchi@tokyo-med.ac.jp
authors.forename: Toru
authors.initials: T
authors.lastname: Kiguchi
authors.forename: Yuta
authors.initials: Y
authors.lastname: Yoshino
authors.forename: Bo
authors.initials: B
authors.lastname: Yuan
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Yoshizawa
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kitahara
authors.forename: Daigo
authors.initials: D
authors.lastname: Akahane
authors.forename: Moritaka
authors.initials: M
authors.lastname: Gotoh
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Kaise
authors.forename: Hiroo
authors.initials: H
authors.lastname: Toyoda
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ohyashiki
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000097:blood / Q000134:cerebrospinal fluid* / Q000627:therapeutic use; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000097:blood / Q000134:cerebrospinal fluid* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000097:blood / Q000134:cerebrospinal fluid* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D000077237:Arsenic Trioxide