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. 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. 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. 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. The https://www.isrctn.com/ identifier is ISRCTN80601124.
Hronová et al. (Mon,) studied this question.