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The assessment of human regional drug absorption of free acid and sodium salt forms of Acipimox, in healthy volunteers, to direct modified release formulation strategy
Author(s) -
Me Rajeev,
Cefali Eugenio,
Wilding Ian,
Wray Heather,
Connor Alyson
Publication year - 2009
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.683
Subject(s) - bioavailability , pharmacology , absorption (acoustics) , dyslipidemia , dosage form , chemistry , drug , pharmacokinetics , crossover study , sodium , medicine , diabetes mellitus , endocrinology , placebo , physics , alternative medicine , organic chemistry , pathology , acoustics
Acipimox is an analog of nicotinic acid and is indicated for the treatment of dyslipidemia. It is also believed to improve glucose control by enhancing insulin sensitivity. The purpose of this study was to direct modified release (MR) formulation strategy by comparing the bioavailability of two forms of acipimox (free acid and sodium salt) from the distal small bowel (DSB) and colon with an immediate release formulation. Two parallel groups of healthy volunteers completed an open label, non‐randomized, three‐way crossover study. The rate and extent of acipimox absorption was highest following administration of the immediate release capsules, and was not influenced by the form of the drug administered. Following administration to the DSB, the relative bioavailability was approximately 52% and 30% for the salt form and free acid form, respectively. Following administration to the colon, the extent of absorption was further reduced. The data indicate that bioavailability from the DSB was limited by the solubility of the drug coupled with an absorption window, whilst absorption from the colon was limited by permeability. The study provided detailed information to support and guide the formulation strategy for a MR form of acipimox, which may improve the treatment of adult patients with type II diabetes and dyslipidemia. Copyright © 2009 John Wiley & Sons, Ltd.