|
Clinical Pharmacology
CLINICAL PHARMACOLOGY
Pharmacodynamics Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. The mode of therapeutic action in Attention Deficit Hyperactivity Disorder (ADHD) is not known. Amphetamines are thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. Text Continues Below
Pharmacokinetics Pharmacokinetic studies of ADDERALL XRª have been conducted in healthy adult and pediatric (6-12 yrs) subjects, and pediatric patients with ADHD. Both ADDERALL ® (immediate-release) tablets and ADDERALL XRª capsules contain d-amphetamine and l-amphetamine salts in the ratio of 3: 1. Following administration of ADDERALL ® (immediate-release), the peak plasma concentrations occurred in about 3 hours for both d-amphetamine and l-amphetamine. The time to reach maximum plasma concentration (T max ) for ADDERALL XRª is about 7 hours, which is about 4 hours longer compared to ADDERALL ® (immediate-release). This is consistent with the extended-release nature of the product. Figure 1 Mean d-amphetamine and l-amphetamine plasma concentrations following administration of ADDERALL XRª 20 mg (8 am) and ADDERALL ® (immediate-release) 10 mg bid (8 am and 12 noon) in the fed state. A single dose of ADDERALL XRª 20 mg capsules provided comparable plasma concentration profiles of both d-amphetamine and l-amphetamine to ADDERALL ® (immediate-release) 10 mg bid administered 4 hours apart. The mean elimination half-life is 1 hour shorter for d-amphetamine and 2 hours shorter for l-amphetamine in children aged 6 to 12 years compared to that in adults (t1/ 2 is 10 hours for d-amphetamine and 13 hours for l-amphetamine in adults, and 9 hours and 11 hours, respectively, for children). ADDERALL XRª demonstrates linear pharmacokinetics over the dose range of 10 to 30 mg. There is no unexpected accumulation at steady state. Page: 1 | 2 | 3 | 4 | Next >>
|
.gif)
