Pharmacokinetics of Apixaban in Patients Undergoing Pancreaticoduodenectomy (PAP-UP)

Abstract

Abstract Background: The impact of pancreaticoduodenectomy (PD) on absorption of drugs in the duodenum remains largely unknown. We aim to characterize the pharmacokinetics of apixaban in patients who have previously underwent PD. Methods: A single 10 mg dose of apixaban was administered to four volunteers who underwent PD at least 6 months prior. The maximum plasma apixaban concentration (Cmax) and area under the plasma concentration time-curve (AUC0-24, AUC0-inf) were compared against healthy historical control subjects (N=12). Geometric mean ratios (GMR) with 90% confidence interval (CI) were calculated for determination of comparative bioequivalence. Results: In PD patients AUC0-24 and AUC0-inf were 1861 and 2080 ng•hr/mL, respectively. The GMRs of AUC0-24 and AUC0-inf between study subjects and healthy controls were 1.27 (90% CI 0.88-1.83) and 1.18 (90% CI 0.82-1.72). The mean Cmax of apixaban was 201 ng/mL (SD 15.6) occurring at a median Tmax of 3.25 hours (range 2.5-4 hours). The GMR of Cmax between study subjects and healthy controls was 1.12 (90% CI 0.77-1.63). Conclusions: The pharmacokinetic characteristics of apixaban in subjects who have undergone PD are not significantly different from those of healthy controls. No changes in their dosing regimen are recommended. ClinicalTrials.gov Identifier: NCT04191928