Relative Bioavailability of Apixaban Solution or Crushed Tablet Formulations Administered by Mouth or Nasogastric Tube in Healthy Subjects

Clin Ther. 2015 Aug;37(8):1703-12. doi: 10.1016/j.clinthera.2015.05.497. Epub 2015 Jul 15.


Purpose: Crushed tablet and solution formulations of apixaban administered orally or via a nasogastric tube (NGT) may be useful in patients unable to swallow solid dose formulations. It is important to understand whether new formulations and/or methods of administration impact apixaban bioavailability and pharmacokinetic properties. These studies evaluated the relative bioavailability (Frel) of apixaban solution administered orally; oral solution administered via NGT flushed with either 5% dextrose in water (D5W) or with infant formula; oral solution via NGT with a nutritional supplement; and crushed tablet suspended in D5W and administered via NGT.

Methods: Three open-label, randomized, crossover studies were conducted in healthy adults (study 1: apixaban 10-mg tablet [reference] versus oral solution, both administered PO; study 2: apixaban 5-mg oral solution PO [reference] versus oral solution via NGT flushed with either D5W or infant formula; study 3: apixaban 5-mg oral solution PO [reference] versus apixaban 5-mg oral solution via NGT with a nutritional supplement and versus crushed tablet suspended in D5W and administered via NGT). Point estimates and 90% CIs of the geometric mean ratios (GMRs; test/reference) were generated for Cmax and AUC. Adverse events were recorded throughout each study.

Findings: Frel of the oral solution was 105% versus tablet, and Frel for oral solution via NGT with D5W flush, infant formula flush, nutritional supplement, and crushed tablet via NGT versus oral solution administration were 96.7%, 92.2%, 81.3%, and 95.1%, respectively. The 90% CIs of the GMRs of all AUCs met the bioequivalence criterion except that of the nutritional supplement (0.766-0.863). The corresponding GMRs for Cmax were 0.977, 0.953, 0.805, 0.682, and 0.884. For the solution via NGT flushed with D5W and for the crushed tablet, the 90% CIs of the Cmax GMRs met the bioequivalence criterion. Apixaban was well tolerated in all 3 studies; most adverse events were mild.

Implications: Comparable Frel was observed for oral apixaban solution, tablet, NGT administration of solution flushed with D5W and infant formula, and NGT administration of crushed tablet suspension. Exposure was less when oral solution was administered via NGT with nutritional supplement. These results support several alternative methods of administering apixaban that may be useful in certain clinical situations. identifiers: NCT02034565, NCT02034578, and NCT02034591.

Keywords: apixaban; bioavailability; crushed tablet; nasogastric tube.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Area Under Curve
  • Atrial Fibrillation / blood
  • Atrial Fibrillation / prevention & control*
  • Biological Availability
  • Chemistry, Pharmaceutical
  • Cross-Over Studies
  • Factor Xa Inhibitors / administration & dosage*
  • Factor Xa Inhibitors / chemistry
  • Factor Xa Inhibitors / pharmacokinetics
  • Factor Xa Inhibitors / pharmacology
  • Female
  • Humans
  • Intubation, Gastrointestinal
  • Male
  • Middle Aged
  • Pyrazoles / administration & dosage*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacokinetics
  • Pyrazoles / pharmacology
  • Pyridones / administration & dosage*
  • Pyridones / chemistry
  • Pyridones / pharmacokinetics
  • Pyridones / pharmacology
  • Treatment Outcome
  • Young Adult


  • Factor Xa Inhibitors
  • Pyrazoles
  • Pyridones
  • apixaban

Associated data