Lisdexamfetamine
Discover related
4 sources
Collated from PsychonautWiki, Pharmacology, DrugCentral, DailyMed. Where sources differ (e.g. dosing), Compare shows them side by side.
Also known as Lisdexamfetamine, Vyvanse, ElvansePW
Oral
Route dataPsychonautWiki
| Threshold | Light | Common | Strong | Heavy |
|---|---|---|---|---|
| 10 mg | 20–30 mg | 30–60 mg | 60–90 mg | 90 mg+ |
| Onset | 60–90 minutes |
|---|---|
| Come-up | 30–60 minutes |
| Peak | 3–5 hours |
| Offset | 4–6 hours |
| Total | 10–14 hours |
| After-effects | 2–6 hours |
Caution / uncertainPW
🧬 Receptor activityDC
| Target | Action | Affinity | Source | |
|---|---|---|---|---|
| Sodium-dependent dopamine transporter (SLC6A3) | Releasing agent | — | DRUGCENTRAL | TargetSodium-dependent dopamine transporter (SLC6A3) ActionReleasing agent Affinity— SourceDRUGCENTRAL |
| Sodium-dependent noradrenaline transporter (SLC6A2) | Releasing agent | — | DRUGCENTRAL | TargetSodium-dependent noradrenaline transporter (SLC6A2) ActionReleasing agent Affinity— SourceDRUGCENTRAL |
| Synaptic vesicular amine transporter (SLC18A2) | Inhibitor | — | DRUGCENTRAL | TargetSynaptic vesicular amine transporter (SLC18A2) ActionInhibitor Affinity— SourceDRUGCENTRAL |
Mechanism of actionPHDM
Lisdexamfetamine is a prodrug of dextroamphetamine, which is a noncatecholamine sympathomimetic amine with CNS stimulant activity. Dextroamphetamine is a known inhibitor of the dopamine transporter (DAT), noradrenaline transporter (NET) and vesicular monoamine transporter 2 (VMAT2), with a weaker affinity for the serotonin transporter (SERT). It is also a weak monoamine oxidase (MAO) inhibitor. Dextroamphetamine ultimately blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and increases catecholamine availability in the extracellular space. The exact mode of therapeutic action of lisdexamfetamine in ADHD and BED has not been fully elucidated; however, the clinical effects of lisdexamfetamine are believed to be linked to the pharmacological actions of dextroamphetamine.
Lisdexamfetamine is a prodrug of dextroamphetamine. Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. Amphetamines block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. The parent drug, lisdexamfetamine, does not bind to the sites responsible for the reuptake of norepinephrine and dopamine in vitro.
PharmacodynamicsPHDM
Once administered, lisdexamfetamine is converted to its active metabolite, dextroamphetamine, which is taken up by the brain. Dextroamphetamine blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and increases the release of these monoamines into the extraneuronal space. The parent drug, lisdexamfetamine, does not bind to the sites responsible for the reuptake of norepinephrine and dopamine in vitro.
Pharmacokinetics
Half-lifePH
Plasma concentrations of unconverted lisdexamfetamine are low and transient, generally becoming non-quantifiable by 8 hours after administration. The plasma elimination half-life of lisdexamfetamine typically averaged less than one hour in volunteers ages six years and older. The plasma elimination half-life of dextroamphetamine was approximately 8.6 to 9.5 hours in pediatric patients six to 12 years and 10 to 11.3 hours in healthy adults.
The plasma elimination half-life of lisdexamfetamine typically averaged less than one hour in studies of lisdexamfetamine dimesylate in volunteers.
AbsorptionPHDM
After oral administration, lisdexamfetamine dimesylate is rapidly absorbed from the gastrointestinal tract. Following single-dose oral administration of lisdexamfetamine in pediatric patients with ADHD under fasted conditions, Tmax of lisdexamfetamine and dextroamphetamine was reached at approximately one hour and 3.5 hours post-dose, respectively. Weight/Dose normalized AUC and Cmax values were the same in pediatric patients as the adults. Food prolongs Tmax by approximately one hour and may decrease the exposure (Cmax and AUC) of dextroamphetamine.
Following oral administration of a 70 mg dose of radiolabeled lisdexamfetamine dimesylate in six healthy subjects, approximately 96% of the oral dose radioactivity was recovered in the urine, and only 0.3% recovered in the feces over 120 hours. Of the radioactivity recovered in the urine, 42% of the dose was related to amphetamine, 25% to hippuric acid, and 2% to intact lisdexamfetamine.
Dextroamphetamine, the active metabolite of lisdexamfetamine, easily crosses the blood-brain barrier.
After oral administration, lisdexamfetamine is rapidly absorbed from the gastrointestinal tract.
Following the oral administration of a 70 mg dose of radiolabeled lisdexamfetamine dimesylate to 6 healthy subjects, approximately 96% of the oral dose radioactivity was recovered in the urine and only 0.3% recovered in the feces over a period of 120 hours. Of the radioactivity recovered in the urine, 42% of the dose was related to amphetamine, 25% to hippuric acid, and 2% to intact lisdexamfetamine. Plasma concentrations of unconverted lisdexamfetamine are low and transient, generally becoming non-quantifiable by 8 hours after administration.
/MILK/ Distributed into milk ... .
MetabolismPH
Lisdexamfetamine dimesylate is hydrolyzed by red blood cells to dextroamphetamine and l-lysine primarily in the blood. Substantial hydrolysis occurs even at low hematocrit levels. Dextroamphetamine can further be metabolized to form other metabolites, such as hippuric acid. Lisdexamfetamine is not metabolized by cytochrome P450 enzymes.
The metabolic route of lisdexamfetamine is unusual because after absorption into the bloodstream it is metabolized by red blood cells to yield d-amphetamine and the natural amino acid, L-lysine, by rate- limited, enzymatic hydrolysis.
Lisdexamfetamine is converted to dextroamphetamine and l-lysine primarily in blood due to the hydrolytic activity of red blood cells. In vitro data demonstrated that red blood cells have a high capacity for metabolism of lisdexamfetamine; substantial hydrolysis occurred even at low hematocrit levels (33% of normal). Lisdexamfetamine is not metabolized by cytochrome P450 enzymes.
These studies investigated the absorption and metabolic conversion of lisdexamfetamine dimesylate (LDX), a prodrug stimulant that requires conversion to d-amphetamine for activity. Oral absorption of LDX was assessed in rat portal and jugular blood, and perfusion of LDX into isolated intestinal segments of anesthetized rats was used to assess regional absorption. Carrier-mediated transport of LDX was investigated in Caco-2 cells and Chinese hamster ovary (CHO) cells expressing human peptide transporter-1 (PEPT1). LDX metabolism was studied in rat and human tissue homogenates and human blood fractions. LDX was approximately10-fold higher in portal blood versus systemic blood. LDX and d-amphetamine were detected in blood following perfusion of the rat small intestine but not the colon. Transport of LDX in Caco-2 cells had permeability apparently similar to cephalexin and was reduced with concurrent PEPT1 inhibitor. Affinity for PEPT1 was also demonstrated in PEPT1-transfected CHO cells. LDX metabolism occurred primarily in whole blood (rat and human), only with red blood cells. Slow hydrolysis in liver and kidney homogenates was probably due to residual blood. The carrier-mediated absorption of intact LDX, likely by the high-capacity PEPT1 transporter, and subsequent metabolism to d-amphetamine in a high-capacity system in blood (ie, red blood cells) may contribute to the consistent, reproducible pharmacokinetic profile of LDX.
Plan a dose of Lisdexamfetamine
Loading the fact-sheet…
Logging a dose needs somewhere to keep it. Start a free session — no signup; it and everything in it expire in 7 days.
External links
Fact-sheets from PsychonautWiki. Harm-reduction reference only — not medical advice.