Steady-state clinical pharmacokinetics of bupropion extended-release in youths

J Am Acad Child Adolesc Psychiatry. 2006 Dec;45(12):1503-9. doi: 10.1097/01.chi.0000237704.05143.bd.

Abstract

Objective: To examine in children and adolescents the 24-hour, steady-state clinical pharmacokinetics of an extended-release (XL) formulation of bupropion (Wellbutrin XL).

Method: Subjects were six male and four female patients (ages 11.5-16.2 years) prescribed bupropion XL in morning daily doses of either 150 mg (n = 5) or 300 mg (n = 5) for at least 14 days. During an overnight hospitalization, subjects had serial blood draws every 1.5 to 3 hours from an intravenous port to measure plasma levels of bupropion and its metabolites. Pharmacokinetic variables were determined by noncompartmental analysis for bupropion and exponential analyses for metabolites.

Results: Bupropion and metabolites demonstrated linear pharmacokinetics. Bupropion's mean maximum concentration (Cmax) was lower (p = .021) and its mean time to Cmax longer (p = .057) in the current sample on bupropion XL relative to a previously studied sample of youths on bupropion sustained-release (Wellbutrin SR). Mean 24-hour area under the curve ratios of metabolites to bupropion ranged from 1.0 for erythrohydrobupropion to 16.4 for hydroxybupropion.

Conclusions: Once-daily dosing is justified in youths prescribed bupropion XL. The active metabolite hydroxybupropion probably has key pharmacodynamic effects, given its higher and more sustained levels relative to the other metabolites or to bupropion.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Antidepressive Agents, Second-Generation / administration & dosage
  • Antidepressive Agents, Second-Generation / pharmacokinetics*
  • Antidepressive Agents, Second-Generation / therapeutic use*
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Bupropion / blood
  • Bupropion / pharmacokinetics*
  • Bupropion / therapeutic use*
  • Child
  • Cytochrome P-450 CYP2B6
  • Cytochrome P-450 CYP3A / metabolism
  • Cytochrome P-450 Enzyme System / metabolism
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / therapeutic use
  • Depressive Disorder, Major / drug therapy*
  • Female
  • Humans
  • Male

Substances

  • Antidepressive Agents, Second-Generation
  • Delayed-Action Preparations
  • Bupropion
  • Cytochrome P-450 Enzyme System
  • CYP2B6 protein, human
  • Cytochrome P-450 CYP2B6
  • Cytochrome P-450 CYP3A