Population pharmacokinetic and exposure-response analyses of guanfacine in Japanese pediatric ADHD patients

Drug Metab Pharmacokinet. 2019 Dec;34(6):365-371. doi: 10.1016/j.dmpk.2019.07.001. Epub 2019 Jul 4.


Guanfacine hydrochloride extended-release tablet (GXR) is approved for child and adolescent patients with attention-deficit/hyperactivity disorder (ADHD). The aims of this study were to develop a population pharmacokinetic model of guanfacine after administration of GXR and to evaluate factors influencing the pharmacokinetics of guanfacine in pediatric ADHD patients. A population pharmacokinetic analysis was performed using 3231 plasma concentration data items of guanfacine for pediatric ADHD patients aged 6-17 years obtained from clinical studies in Japan and the US. In addition, the relationship of the ADHD Rating Scale IV (ADHD RS-IV, efficacy endpoint) total score with exposure to guanfacine was assessed for Japanese pediatric ADHD patients. A one-compartment model with first-order absorption and lag time well described the plasma concentration data of guanfacine in pediatric ADHD patients. Body weight was selected as a covariate of apparent total body clearance and apparent volume of distribution. There was no pharmacokinetic difference between Japanese and non-Japanese pediatric ADHD patients. The results suggested a tendency of exposure-dependent reduction in the ADHD RS-IV total score, whereas the reduction was observed even at low plasma exposure levels compared with the placebo group.

Keywords: ADHD; Exposure-response; Guanfacine; Pediatric; Population pharmacokinetics.

MeSH terms

  • Adolescent
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Attention Deficit Disorder with Hyperactivity / metabolism
  • Child
  • Female
  • Guanfacine / blood*
  • Guanfacine / pharmacokinetics*
  • Humans
  • Male


  • Guanfacine