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ABSTRACT
This article reviews the unique prodrug stimulant lisdexamfetamine dimesylate (LDX, Vyvanse®), an approved treatment for attention-deficit/hyperactivity disorder. LDX is an inactive prodrug in which l-lysine is chemically bonded to d-amphetamine. Although its efficacy is not significantly different from that of other stimulants, LDX may be different with respect to potential toxicity and abuse liability. In this article, I will review the short-term controlled studies that were the basis for LDX's approval for both children and adults; the lack of and need for more long-term studies; two double-blind, placebo-controlled, crossover studies that examined LDX's abuse liability; and clinical uses for the drug. The clinical implications stemming from LDX's unique characteristics are also discussed.
Various stimulant drug formulations, such as methylphenidate (Ritalin ®, Concerta®, and others) and amphetamine (Dexedrine®, Adderall ®, and others) products, are the most commonly prescribed medications for attention-deficit/hyperactivity disorder (ADHD) (Findling, 2008). In this article, I review the unique prodrug stimulant lisdexamfetamine dimesylate (LDX, Vyvanse®), which is a U.S. Food and Drug Administration (FDA)-approved treatment for ADHD in children and adults.
WHAT IS LISDEXAMFETAMINE?
Prodrugs are pharmacologically inactive compounds, designed to maximize the amount of the active component of the prodrug that ultimately reaches its site of action (Hardman, Limbird, Molinoff, Ruddon, & Gilman, 1996). Inactive prodrugs work therapeutically when they are converted to biologically active metabolites. LDX is an inactive prodrug in which d-amphetamine (dextroamphetamine or DEX, Dexedrine ®) is chemically bonded to l-lysine, an essential amino acid (Krishnan & Montcrief, 2007a). After oral ingestion, the bond is metabolically cleaved, LDX is converted to l-lysine and to the pharmacologically active DEX, and unconverted LDX serum concentrations are very low.
When LDX is administered parenterally, minimal amounts of DEX are released. Although the LDX conversion enzyme(s) are unknown, this confirms that the biotransformation occurs in the gastrointestinal tract. Compared with orally ingested DEX, exposure to LDX-released DEX is decreased and delayed after intravenous or intranasal LDX administration and with very high oral LDX dosages (above therapeutic amounts). Pharmacokinetic studies show that DEX is released from LDX in an extended-release pattern, suggesting that the metabolic conversion of LDX is a rate-limited process (Krishnan & Stark, 2008).
SHORT-TERM STUDIES
In February 2007, the FDA approved LDX for ADHD in children ages 6 to...