Population Pharmacokinetic Modeling of Guanfacine in Pediatric Patients
William Knebel1, Mary Corcoran, James Ermer
1Metrum Research Group LLC, 2 Tunxis Road, Suite 112, Tariffville, CT, 06081, USA, billk@metrumrg.com.
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.
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