In vitro studies of amphetamine and its metabolites indicate minor inhibition of CYP2D6, 1A2, and 3A4. 1 Any drug interactions associated with LDX are thought to be secondary to amphetamine and its metabolites and not to intact LDX. 2 Intact LDX does not utilize the cytochrome P450 enzymes for metabolism. The other active metabolite of MAS XR is norephedrine. 1, 2 The enzymes involved in MAS XR metabolism have not been clearly defined however, CYP2D6 is known to be responsible for the formation of one of the MAS XR active metabolites, 4-hydroxy-amphetamine. While food does not affect the extent of absorption for either medication, it has been shown to prolong the time to maximum concentration by 2.5 hours for MAS XR and 1 hour for LDX. 1 Both MAS XR and LDX display linear pharmacokinetics in a dosage range of 5–30 mg and 30–70 mg in children 6–12 years of age. 5 LDX reaches its peak plasma concentration in approximately 1 hour while the active medication, dextroamphetamine, reaches a peak plasma concentration in approximately 3.5 hours. 4 This conversion is proposed to occur primarily (90%) in systemic circulation. After oral administration, LDX is cleaved into L-lysine, an essential amino acid, and dextroamphetamine. A prodrug is a product that when initially administered is inactive but then undergoes biotransformation in the body to have a therapeutic effect. 2 The long acting property of LDX is secondary to it being a prodrug of dextroamphetamine making it the only prodrug stimulant. 3 MAS XR reaches its peak plasma concentration in approximately 7 hours, which is consistent with its extended release properties. Half of the beads in the MAS XR capsule are immediate release while the other half are extended release.
3 MAS XR is a bead filled (mixed amphetamine combination) capsule that upon administration mimics twice daily dosing. Long-acting stimulants are considered to be equally efficacious to the short acting stimulants (i.e., immediate release MAS). Both MAS XR and LDX are long-acting, once daily stimulants with a duration of action of approximately 10 hours.