title: 4-oxo retinoic acid for refractory acute promyelocytic leukemia in children with all-trans retinoic acid therapy.
abstract: Therapy with all-trans retinoic acid (ATRA) achieves complete remission in a high proportion of patients with acute promyelocytic leukemia (APL), but the efficacy is reported to relate to plasma ATRA level after oral administration. The pharmacokinetics of ATRA and 4-oxo all-trans retinoic acid (4-oxo ATRA), a metabolite of ATRA, were studied in four children with APL at the time of initial oral administration. After administration of ATRA at a dose of 30 mg/m2, the peak plasma ATRA level was 20-741 ng/ml and was reached at 60-120 min. The patient with the lowest peak plasma level did not achieve complete remission and had a very high 4-oxo ATRA level compared to the patients with complete remission. These findings suggest that accelerated metabolism of ATRA plays a role in the failure of this agent in the patients without remission.
authors.affiliation: Department of Pediatrics, Osaka Medical College, Takatsuki, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takitani
authors.forename: H
authors.initials: H
authors.lastname: Tamai
authors.forename: T
authors.initials: T
authors.lastname: Morinobu
authors.forename: N
authors.initials: N
authors.lastname: Kawamura
authors.forename: M
authors.initials: M
authors.lastname: Miyake
authors.forename: T
authors.initials: T
authors.lastname: Fujimoto
authors.forename: M
authors.initials: M
authors.lastname: Mino
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008297:Male; D014212:Tretinoin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; C002202:4-oxoretinoic acid; D014212:Tretinoin