Clinical Pharmacokinetics

, Volume 54, Issue 8, pp 875–883 | Cite as

Population Pharmacokinetic Modeling of Guanfacine in Pediatric Patients

  • William Knebel
  • Mary Corcoran
  • James Ermer
  • Marc R. Gastonguay
Original Research Article

Abstract

Introduction

The population pharmacokinetics of guanfacine extended release were characterized in pediatric patients aged 6–17 years using NONMEM and evaluated by predictive check and bootstrap.

Methods

Data were described using a one-compartment model. A covariate modeling approach that emphasized parameter estimation rather than stepwise hypothesis testing was implemented. A nonparametric bootstrap procedure and a predictive check method were used to evaluate the final model and parameter estimates.

Results

Typical population pharmacokinetic parameters (95 % confidence interval), given the reference covariates (Caucasian, male, age 12 years, weight 50 kg), were 33.1 (30.2–36.4) L/h for apparent clearance (CL/F), 804 (703–900) L for apparent volume of distribution, 0.552 (0.437–0.670) h−1 for the absorption rate constant, and 0.651 (0.608–0.697) h for absorption lag time.

Discussion

The pharmacokinetics of guanfacine are similar in pediatric patients compared with adults when appropriately scaled by patient weight. The main predictor of guanfacine exposure, as determined by a change in CL/F, was weight. Effects of the other covariates (age, sex, and race) on CL/F were estimated with reasonable precision; however, the additional effects of age, sex, and race can be considered to have little to no clinical relevance.

Supplementary material

40262_2015_245_MOESM1_ESM.tiff (1 mb)
Supplemental Fig. 1. Predictive check for median guanfacine concentrations with distributions of simulated median concentrations within each individual (Cmed) compared to the actual observed distribution of Cmed values from the population pharmacokinetic database. Quantile-quantile plots for each of the 1000 simulation replicates are depicted by a grey dashed line and are overlaid on this plot. The black solid line represents a reference line of identity.(TIFF 1054 kb)

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • William Knebel
    • 1
  • Mary Corcoran
    • 2
  • James Ermer
    • 2
  • Marc R. Gastonguay
    • 1
  1. 1.Metrum Research Group LLCTariffvilleUSA
  2. 2.Shire Development LLCWayneUSA

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