Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine

Michael PennickBiosciences Department, Shire Pharmaceutical Development Ltd, Basingstoke, UKAbstract: 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 o...

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Autor principal:	Michael Pennick
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2010
Materias:	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/50dcc49742e546ef94b5dfbec870a8c2
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spelling	oai:doaj.org-article:50dcc49742e546ef94b5dfbec870a8c22021-12-02T02:45:58ZAbsorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine1176-63281178-2021https://doaj.org/article/50dcc49742e546ef94b5dfbec870a8c22010-06-01T00:00:00Zhttp://www.dovepress.com/absorption-of-lisdexamfetamine-dimesylate-and-its-enzymatic-conversion-a4556https://doaj.org/toc/1176-6328https://doaj.org/toc/1178-2021Michael PennickBiosciences Department, Shire Pharmaceutical Development Ltd, Basingstoke, UKAbstract: 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.Keywords: lisdexamfetamine dimesylate, LDX, prodrug, ADHD, absorption, Vyvanse Michael PennickDove Medical PressarticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol 2010, Iss Issue 1, Pp 317-327 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Michael Pennick Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine
description	Michael PennickBiosciences Department, Shire Pharmaceutical Development Ltd, Basingstoke, UKAbstract: 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.Keywords: lisdexamfetamine dimesylate, LDX, prodrug, ADHD, absorption, Vyvanse
format	article
author	Michael Pennick
author_facet	Michael Pennick
author_sort	Michael Pennick
title	Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine
title_short	Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine
title_full	Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine
title_fullStr	Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine
title_full_unstemmed	Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine
title_sort	absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine
publisher	Dove Medical Press
publishDate	2010
url	https://doaj.org/article/50dcc49742e546ef94b5dfbec870a8c2
work_keys_str_mv	AT michaelpennick absorptionoflisdexamfetaminedimesylateanditsenzymaticconversiontodamphetamine
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Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine

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