Lisdexamfetamine

Drugbox
IUPAC_name = ("S")-2,6-diamino-N- [("S")-1-phenylpropan-2-yl] hexanamide


width=192px
CAS_number= 608137-32-2
ATC_prefix=
ATC_suffix=
PubChem= 11597697
DrugBank=
C=15 | H=25 | N=3 | O=1
molecular_weight = 263.378 g/mol
bioavailability=
metabolism = Hepatic
elimination_half-life= < 1 hour (prodrug molecule)
excretion = Renal: ~2%
pregnancy_category = C
legal_US = Schedule II
legal_status =
routes_of_administration= Oral

Lisdexamfetamine (L-lysine-d-amphetamine) is an inactive molecule prodrug (brand name Vyvanse) consisting of the psychostimulant d-amphetamine coupled with the essential amino acid L-lysine. Lisdexamfetamine was developed so that the psychostimulant is released and activated more slowly as the prodrug molecule is hydrolyzed—consequently cleaving off the amino acid-during the first pass through the intestines and/or the liver. Essentially, this makes lisdexamfetamine an extended-release formulation of d-amphetamine; however, the release characteristics are integral to the molecule itself, rather than simply the pill construction.

Vyvanse is the dimesylate salt of lisdexamfetamine, developed by New River Pharmaceuticals, who were bought by Shire Pharmaceuticals shortly before lisdexamfetamine began marketing. It is marketed by Shire Pharmaceuticals. Vyvanse is FDA approved for the treatment of attention-deficit hyperactivity disorder in pediatric patients ages 6–12, and in adults. Vyvanse pills are available in dosages of up to 70mg. Not only does Shire aspire to have Vyvanse replace Adderall XR as their flagship ADHD product,Fact|date=September 2008 they also have their marketing target set at 50% of the ADHD pharmaceutical market share.Fact|date=September 2008 Shire will be applying for European approval for the treatment of adolescents and adult ADHD patients, and for adolescent FDA approval.Fact|date=September 2008 Unlike Adderall, which contains roughly 75% d-amphetamine and 25% l-amphetamine, lisdexamfetamine is a single-enantiomer amphetamine formulation. Certain individuals exhibit a better clinical response to the mixed isomer preparation, thus they may continue to use Adderall XR or equivalent generics.

A 25 mg Vyvanse capsule is molecularly equivalent to a 10 mg Dexedrine Spansule (both the aforementioned pharmaceuticals are about 7.425 mg dextroamphetamine), although a 25mg Vyvanse capsule is not commercially available (see dosage strengths below). However, this molecular equivalence ratio does not imply that these respective doses of Vyvanse and Dexedrine XR (Spansule) are bioequivalent--the two formulations have slightly different pharmacokinetic profiles. That is, while the AUC for the aforementioned pharmaceuticals is equivalent, the peak exposure (C_max) to the active compound dextroamphetamine is about 50% higher for Vyvanse than for Dexedrine XR. [ [http://www.fda.gov/cder/foi/nda/2007/021977s000_ClinPharmR.pdf FDA Approval of Vyvanse - Pharmacological Reviews] ]

In human oral abuse-liability studies, 150 mg Vyvanse produced a "likeability"—euphoric effect—that was determined to be indistinguishable from 200 mg of the Schedule IV drug diethylpropion hydrochloride or 40 mg of dextroamphetamine. [ [http://www.vyvanse.com/pdf/prescribing_information.pdf VyvstdfullPILDXPI9 (Page 1) ] ]

On January 3rd, 2008, Shire Pharmaceuticals announced that the FDA approved three new dosage strengths of 20, 40, and 60 milligrams. These new dosages will supplement the 30, 50, and 70 milligram dosages that are already available. [ [http://www.boston.com/business/healthcare/articles/2008/01/03/shire_fda_oks_new_vyvanse_dosages/ Shire: FDA OKs new Vyvanse dosages - Boston.com ] ] On April 23rd, 2008, Vyvanse received FDA approval for the adult population. [ [http://www.fda.gov/cder/foi/appletter/2008/021977s001ltr.pdf FDA Adult Approval of Vyvanse - FDA Label and Approval History] ]

Notes and references

http://www.vyvanse.com