| Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine. | |
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MedLine Citation:
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PMID: 20628632 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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. |
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Authors:
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Michael Pennick |
Publication Detail:
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Type: Journal Article Date: 2010-06-24 |
Journal Detail:
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Title: Neuropsychiatric disease and treatment Volume: 6 ISSN: 1178-2021 ISO Abbreviation: Neuropsychiatr Dis Treat Publication Date: 2010 |
Date Detail:
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Created Date: 2010-07-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101240304 Medline TA: Neuropsychiatr Dis Treat Country: New Zealand |
Other Details:
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Languages: eng Pagination: 317-27 Citation Subset: - |
Affiliation:
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Biosciences Department, Shire Pharmaceutical Development Ltd, Basingstoke, UK. |
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