Regional Gastrointestinal Absorption of Apixaban in Healthy Subjects

Abstract This study was conducted to investigate the extent of absorption in different regions of the gastrointestinal (GI) tract. The relative bioavailability of an apixaban crushed tablet was also assessed to investigate the effect of dissolution on absorption. This was an open‐label, randomized, 4‐period, 4‐treatment crossover study with a 7‐day washout period balanced for first‐order residual effects in 12 healthy subjects. Subjects received a single dose of a 2.5‐mg apixaban solution administered orally, released in the distal small intestine and in the ascending colon. In addition, subjects received a single dose of a 2.5‐mg apixaban crushed tablet released in the ascending colon. The solution and crushed tablet were delivered via Enterion capsules. The location of Enterion capsules was monitored using scintigraphic imaging. Apixaban maximum observed plasma concentration (C max ) and area under the plasma concentration–time curve from zero to the time of the last quantifiable concentration (AUC 0–t ) decreased by approximately 60% when it was delivered to the distal small bowel compared with the oral administration. A greater decrease was observed when it was delivered to the ascending colon, with reductions of 90% and 84% in C max and AUC 0–t , respectively. A crushed tablet delivered to the ascending colon resulted in exposure that was approximately 40% of that observed for solution released in the same region. These findings indicate that apixaban exhibits region‐dependent absorption and that dissolution/solubility of the solid‐dose form is limited in the ascending colon. Apixaban absorption decreased progressively along the GI tract, indicating that absorption occurs primarily in the upper GI tract.