An Oral Human Drug Absorption Study to Assess the Impact of Site of Delivery on the Bioavailability of Bevirimat

Bevirimat is a first in class, orally active, potent and selective inhibitor of HIV‐1. It may have utility for the treatment of HIV‐1‐infected patients who are failing current regimens because of the development of drug resistance. In earlier studies in HIV‐1‐infected patients, an immediate‐release tablet formulation exhibited a relative bioavailability (Frel) of 50% or greater and a higher intersubject variability than an oral solution. The purpose of this study was to determine whether this pharmacokinetic profile is attributable to a narrow permeability‐dependent absorption window within the gastrointestinal tract. Three groups of subjects completed an open‐label, 2‐way crossover, randomized pharmacoscintigraphic study. Subjects received a 25‐mg bevirimat oral immediate‐release solution plus 25 mg bevirimat solution delivered to the proximal small bowel, distal small bowel, or colon via the Enterion™ capsule. The results indicate that the permeability of bevirimat throughout the small intestine was excellent and suggest that the variability observed for the immediate release tablet was not related to the presence of an absorption window in the small intestine.