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.