Pharmacokinetics of apixaban in patients with short bowel syndrome: a Bayesian re-estimation approach.

BACKGROUND

Short bowel syndrome (SBS) is a malabsorptive condition that may impair drug absorption, including direct oral anticoagulants such as apixaban. This study aimed to assess whether the pharmacokinetics (PK) of apixaban in patients with SBS differs from those observed in individuals with an intact gastrointestinal (GI) tract, using Bayesian re-estimation with an existing population PK (pop PK) model.

RESEARCH DESIGN AND

METHODS

Thirteen patients with SBS (7 males, 6 females; median age 79 years, weight 76 kg, eGFR 53 mL/min) receiving apixaban (2.5-7.5 mg twice daily) contributed 69 steady-state plasma concentrations. Bayesian re-estimation was performed using a previously published pop PK model in NONMEM v7.4. Model fit was evaluated using goodness-of-fit (GOF) plots and the trends in the distribution of individual ETA-values. Fractional differences in absorption parameters - ka and Frel-between the SBS cohort and the reference population were explored.

RESULTS

GOF plots showed no significant bias, and the published model predicted apixaban concentrations in the SBS cohort with acceptable accuracy. Estimated absorption parameters in SBS patients were comparable to those in the original population.

CONCLUSION

In stabilized SBS patients, the absorption of apixaban may not be significantly altered. Standard dosing of apixaban is expected to be appropriate in this population.

CLINICAL TRIAL REGISTRATION: The https://www.isrctn.com/ identifier is ISRCTN80601124.