Multiple dose pharmacokinetics of paroxetine in children and adolescents with major depressive disorder or obsessive-compulsive disorder

Robert L Findling, Gianluca Nucci, Antoni A. Piergies, Roberto Gomeni, Edward I. Bartolic, Regan Fong, David J. Carpenter, J. Steven Leeder, Andrea Gaedigk, Theodore M. Danoff

Research output: Contribution to journalArticle

Abstract

The current study examined the pharmacokinetics (PK), safety, and tolerability of paroxetine after repeated multiple oral dosing in children and adolescents with major depressive or obsessive-compulsive disorder. In this 6-week, open-label, repeat dose, dose-rising study, 62 patients (27 children and 35 adolescents) were treated with paroxetine 10 mg/day for the first 2 weeks of the study, 20 mg/day for the next 2 weeks, and 30 mg/day for the final 2 weeks. Pharmacokinetic sampling and safety assessments occurred at baseline and subsequently on the final treatment day of each dosing level. Between-patient variability in PK was pronounced at the 10 mg dose level, but markedly reduced at higher doses. A supra-proportional increase in plasma concentrations with increasing dose was evident in both age groups. Data for Cmax and AUC(0-24) indicated that, at each dose level, paroxetine steady-state systemic exposure was higher in children than in adolescents. The differences between age groups, however, diminished with each increasing dose, and were virtually abolished when differences in weight among different age groups were considered. Stepwise regression analysis indicated that both oral clearance and volume of distribution were highly dependent on paroxetine dose, cytochrome P4502D6 genotype, and weight (p

Original languageEnglish (US)
Pages (from-to)1274-1285
Number of pages12
JournalNeuropsychopharmacology
Volume31
Issue number6
DOIs
StatePublished - Jun 2006
Externally publishedYes

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Paroxetine
Obsessive-Compulsive Disorder
Major Depressive Disorder
Pharmacokinetics
Age Groups
Safety
Weights and Measures
Cytochromes
Area Under Curve
Genotype
Regression Analysis
Therapeutics

Keywords

  • Adolescents
  • Children
  • Depression
  • Obsessive-compulsive disorder
  • Paroxetine
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology

Cite this

Multiple dose pharmacokinetics of paroxetine in children and adolescents with major depressive disorder or obsessive-compulsive disorder. / Findling, Robert L; Nucci, Gianluca; Piergies, Antoni A.; Gomeni, Roberto; Bartolic, Edward I.; Fong, Regan; Carpenter, David J.; Leeder, J. Steven; Gaedigk, Andrea; Danoff, Theodore M.

In: Neuropsychopharmacology, Vol. 31, No. 6, 06.2006, p. 1274-1285.

Research output: Contribution to journalArticle

Findling, RL, Nucci, G, Piergies, AA, Gomeni, R, Bartolic, EI, Fong, R, Carpenter, DJ, Leeder, JS, Gaedigk, A & Danoff, TM 2006, 'Multiple dose pharmacokinetics of paroxetine in children and adolescents with major depressive disorder or obsessive-compulsive disorder', Neuropsychopharmacology, vol. 31, no. 6, pp. 1274-1285. https://doi.org/10.1038/sj.npp.1300960
Findling, Robert L ; Nucci, Gianluca ; Piergies, Antoni A. ; Gomeni, Roberto ; Bartolic, Edward I. ; Fong, Regan ; Carpenter, David J. ; Leeder, J. Steven ; Gaedigk, Andrea ; Danoff, Theodore M. / Multiple dose pharmacokinetics of paroxetine in children and adolescents with major depressive disorder or obsessive-compulsive disorder. In: Neuropsychopharmacology. 2006 ; Vol. 31, No. 6. pp. 1274-1285.
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