Immediate-release guanfacine is well absorbed, with an oral bioavailability of approximately 80%. Peak concentrations occur 1-4 hours after an oral dose. It has a large volume of distribution, 6.3 L/kg, reflecting extensive distribution throughout the body. Guanfacine is metabolized via hepatic conjugation. The parent compound and metabolites are excreted in the urine. The elimination half-life of immediate-release guanfacine is approximately 10 to 17 hours in adults.
In 2007, Swearingen and colleagues conducted a Phase I open-label single-dose pharmacokinetic study of extended-release guanfacine in 52 adults. The maximum serum concentrations (Cmax) ranged from 0.98±0.26 ng/mL with a 1 mg dose to 3.58±1.39 ng/mL with the 4 mg dose. Area under the concentration-time curve (AUC0∞) ranged from 32.4±8.78 ng/mL·h-1 for the 1 mg dose to 124.1±45.1 ng/mL·h-1 for the 4 mg dose. The average elimination half-life ranged from 16.6±3.8 to 17.5±3.8 hours.
The pharmacokinetic profile of extended-release guanfacine was also recently studied in a group of 14 children (6-12 years of age) and 14 adolescents (12-17 years of age). All subjects received a single 2 mg dose on the first day of the study, followed by a wash-out period, then sequential doses of 2 mg, 3 mg, and 4 mg each for a week. After the 2 mg dose, the younger children achieved a higher AUC0-∞, with an average of 62.5±23.9 ng·hr/mL compared to 47.3±13.7 ng·hr/mL in the adolescents. Time to maximum plasma concentration was approximately 5 hours for both age groups. The Cmax increased proportionally to the dose, with the 2 mg dose producing Cmax values of 4.39±1.66 ng/mL and 2.86±0.77 ng/mL in the younger and older groups, respectively. For comparison, a week of treatment with the 4 mg dose produced Cmax values of 10.1±7.09 ng/L and 7.01±1.53 ng/mL. The average elimination half-life was 14.4±2.39 hours in younger children and 17.9±5.77 hours in adolescents.
Pediatr Pharm. 2008;14(4) © 2008 Children's Medical Center, University of Virginia
Cite this: New Treatment Options for Attention-Deficit/Hyperactivity Disorder (ADHD): Part II. Guanfacine - Medscape - Apr 01, 2008.