Population Pharmacokinetic Modeling of Guanfacine in Pediatric Patients
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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.
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.
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.
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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