Paroxetine pharmacokinetics in depressed children and adolescents

Robert L. Findling, Michael D. Reed, Carolyn Myers, Mary Ann O'Riordan, Sandra Fiala, Lisa Branicky, Byron Waldorf, Jeffrey L. Blumer

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To describe the pharmacokinetics and safety of paroxetine in children and adolescents and to explore the role of genetic polymorphisms in paroxetine pharmacokinetics. Method: Thirty depressed youths were enrolled. Samples for phenotyping with respect to cytochrome P450 2D6 (CYP2D6) and catechol-O-methyltransferase were collected. A single 10-mg dose of paroxetine was then administered followed by 5 days of blood and urine collection for pharmacokinetic analyses. Subjects subsequently received open treatment for 8 weeks, and weekly blood samples were obtained for plasma concentration measurements. Results: There was tremendous interindividual variability in paroxetine disposition. The mean half-life of paroxetine was 11.1 ± 5.2 (SD) hours. The average clearance was 88.7 ± 66.4 mL/min/kg. The mean area under the plasma drug concentration curve was 0.09 ± 0.10 μg/mL·hr. Within-subject variability of plasma paroxetine concentrations was generally not significant. Clearance and fractional urinary excretion of paroxetine were found to correlate with CYP2D6 activity. Two subjects developed hypomania necessitating drug discontinuation. No clinically significant changes in any safety assessments were noted. Conclusions: Paroxetine is more rapidly cleared in youths than adults and may be given once daily in this population. Short-term treatment with paroxetine appears safe and well tolerated in this relatively small sample of pediatric patients.

Original languageEnglish (US)
Pages (from-to)952-959
Number of pages8
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Volume38
Issue number8
DOIs
StatePublished - 1999

Keywords

  • Depression
  • Paroxetine
  • Pharmacokinetics

ASJC Scopus subject areas

  • Developmental and Educational Psychology
  • Psychiatry and Mental health

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