Nefazodone pharmacokinetics depressed children and adolescents

Robert L. Findling, Sheldon H. Preskorn, Ronald N. Marcus, Ryan D. Magnus, Frances D'Amico, Punit Marathe, Michael D. Reed

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To describe the pharmacokinetics and safety of nefazodone (NFZ) in depressed children and adolescents. Method: Depressed youths aged 7 to 17 years were eligible to participate. Intensive sampling for pharmacokinetic analyses of NFZ and 3 of its active metabolites was performed after single and multiple dose administration. Treatment was continued for 6 more weeks and titrated to maximize clinical response. Results: Twenty-eight patients were enrolled. Systemic exposure to NFZ and 3 metabotites was generally higher in children than adolescents. NFZ and metabolite disposition profiles showed high intra- and interpatient variability. Compared to published data in adults, the half-life of NFZ and 2 of its metabolites appears shorter in children and adolescents. Meta-chlorphenylpiperazine pharmacokinetic parameters were different in 5 patients determined to be poor metabolizers of cytochrome P450 2D6 (CYP2D6). NFZ was well tolerated, and administration was associated with significant reductions (p angle .001) in depressive symptoms. Conclusions: The pharmacokinetics of NFZ in pediatric patients is highly variable. NFZ appears to be safe in this small, short-term study. Pediatric patients who are poor metabolizers of CYP2D6 do not appear to be at increased risk for NFZ-associated adverse events. Open-label treatment of NFZ is associated with reductions in depressive symptoms.

Original languageEnglish (US)
Pages (from-to)1008-1016
Number of pages9
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Volume39
Issue number8
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Keywords

  • Depression
  • Nefazodone
  • Pharmacokinetics

ASJC Scopus subject areas

  • Developmental and Educational Psychology
  • Psychiatry and Mental health

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