Pharmacology of all-trans-retinoic acid in children with acute promyelocytic leukemia.

摘要: Background Due to severe side effects in virtually all children treated with a standard dose of 45 mg/m2/day all-trans-retinoic acid (ATRA) for acute promyelocytic leukemia (APL) the AML-BFM study group reduced dosage 25 mg/m2/day. For lack data on use ATRA at this APL, further decided evaluate pharmacokinetics and metabolism children. Procedure Twenty-three pharmacokinetic metabolic profiles were studied 14 (aged 0.9–18.4 years) APL. Eleven plasma samples collected over period 8 hr analyzed its metabolites by high-performance liquid chromatography. Results Peak concentrations characterized wide interpatient variability (range: 28.6–513.0 nM). Compared adults same pathways observed children. Even though peak lower range those considered effective vitro, effects, notably neurotoxicity, still required reduction, treatment break, or drug withdrawal eight patients. In small number patients, neurotoxicity could not be related age any specific level plasma. Plasma vitamin A, however, significantly higher who developed signs (P = 0.03, Mann–Whitney Rank Sum test). Conclusions Considering low persistence toxicity spite reduction intermittent dosing schedules might as an alternative APL especially children, risk ATRA-induced neurotoxicity. Med Pediatr Oncol 2003;40:293–301. © 2003 Wiley-Liss, Inc.