O022 - APIXABAN IS A VALID ORAL ANTICOAGULANT IN MOST PATIENTS WITH SHORT BOWEL SYNDROME

O022

APIXABAN IS A VALID ORAL ANTICOAGULANT IN MOST PATIENTS WITH SHORT BOWEL SYNDROME

B. Deleenheer^1,2,3,*, Y. Hoffert⁴, T. Vanassche⁵, L. Wauters^1,3, L. Van der Linden^2,4, E. Dreesen⁴, T. Vanuytsel^1,3

¹Leuven Intestinal Failure and Transplantation (LIFT), ²Hospital Pharmacy, University Hospitals Leuven, ³Department of Chronic Diseases and Metabolism, ⁴Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, ⁵Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium

Rationale: Short bowel syndrome (SBS) patients often need anticoagulation for catheter-related thrombosis or post-mesenteric ischaemia prevention. Oral absorption of apixaban, a commonly used anticoagulant, is uncertain and likely reduced in SBS due to limited surface area and altered transit. The effect of teduglutide on oral drug absorption is unknown. This pharmacokinetic (PK) study evaluates apixaban PK in SBS, its variability and correlations with patient and disease factors.

Methods: Patients with (27 anticoagulant-naive, 7 on chronic 2×5mg apixaban) and without SBS (26 anticoagulant-naive, 10 on chronic 2×5mg apixaban) underwent 24h intensive PK sampling after a 2.5mg and/or 5mg apixaban dose. SBS patients starting teduglutide had sampling repeated after ≥6 months. We assessed exposure (peak plasma concentration, C_max; time to C_max, T_max; area under the curve, AUC) in relation to bowel length, colon presence, parenteral support, loperamide dose and citrulline. We built a population PK model (NONMEM v.7.5) and assessed the same covariate effects on bioavailability (F) and absorption rate constant (Ka).

Results: SBS patients showed reduced C_max (20–82ng/mL lower depending on dosing condition) and AUC (4,800-40,000min∙ng/mL lower) with substantial variability, although mostly within Phase I-III ranges. F and Ka were lower in SBS, with large variability (coefficients of variation 58% and 49%, resp.). Small bowel length (r=0.37-0.51, p=0.007-0.056) and citrulline (r=0.37-0.55, p=0.007-0.056) correlated positively with C_max and AUC and C_max, AUC and F resp. Absorption was faster in patients without a colon (T_max ±2h shorter, p<0.001). After teduglutide initiation, C_max and AUC increased.

Conclusion: Apixaban is a valid oral anticoagulant in SBS, but high variability warrants measuring C_max at least once to confirm adequate exposure. Optimal C_max sampling time may depend on colon presence.Teduglutide increased apixaban exposure.

Disclosure of Interest: None declared