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 ) and area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration (AUC ) 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 and AUC , 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.

Interindividual Variability of Apixaban Plasma Concentrations: Influence of Clinical and Genetic Factors in a Real-Life Cohort of Atrial Fibrillation Patients

“…They had lower apixaban plasma concentrations. Apixaban has low hydrosolubility [40,41], and therefore, the systemic expansion of interstitial fluid that happens in periodic temporary decompensations of heart failure cannot explain the reduced plasma values. Other possible causes could be the systemic arterial hypoperfusion status, venous congestion, and neurohormonal activation, which negatively influences the integrity and function of the key organs, in particular the gastrointestinal tract, liver, and kidneys [42].…”

Apixaban: A Clinical Pharmacokinetic and Pharmacodynamic Review

“…The maximum plasma concentration ( C max ) of apixaban occurs 3–4 h after oral administration [17, 21]. The absorption of apixaban appears to occur primarily in the small intestine and decreases progressively throughout the gastrointestinal tract [22]. Compared with oral administration, the bioavailability of 2.5 mg of apixaban solution was approximately 60% and 84% lower when released in the distal small bowel and ascending colon, respectively [22].…”

“…The absorption of apixaban appears to occur primarily in the small intestine and decreases progressively throughout the gastrointestinal tract [22]. Compared with oral administration, the bioavailability of 2.5 mg of apixaban solution was approximately 60% and 84% lower when released in the distal small bowel and ascending colon, respectively [22]. For oral doses up to 10 mg, the absolute bioavailability of apixaban is ~ 50% [23, 24], resulting from the incomplete absorption [18] and first-pass metabolism in the gut and liver [25, 26].…”

Pharmacokinetics and Pharmacogenetics of Apixaban

“…Максимальная концентрация (C max ) апиксабана в плазме достигается через 3-4 ч после перорального приема [27,28]. Абсорбция апиксабана происходит, главным образом, в тонком кишечнике и постепенно снижается по мере прохождения по нему [29]. Для пероральных доз до 10 мг абсолютная биодоступность апиксабана составляет около 50% из-за неполного всасывания [30,31] и первого прохождения через печень [32,33].…”