Pharmacokinetics of apixaban in patients undergoing pancreaticoduodenectomy (PAP-UP)

Objective: The impact of pancreaticoduodenectomy on absorption of drugs in the duodenum remains largely unknown. We aim to characterize the pharmacokinetics of apixaban in patients who had previously undergone pancreaticoduodenectomy. Materials and methods: A single 10 -mg dose of apixaban was administered to 4 volunteers who underwent pancreaticoduodenectomy at least 6 months prior. The maximum plasma apixaban concentration (Cmax) max ) and area under the plasma concentration time -curve (AUC 0-24, AUC 0-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 pancreaticoduodenectomy patients, AUC 0-24 and AUC 0-inf were 1,861 and 2,080 ngxh/ mL, respectively. The GMRs of AUC 0-24 and AUC 0-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 C max of apixaban was 201 ng/mL (SD 15.6) occurring at a median t max of 3.25 hours (range 2.5 - 4 hours). The GMR of C max between study subjects and healthy controls was 1.12 (90% CI 0.77 - 1.63). Conclusion: The pharmacokinetic characteristics of apixaban in subjects who had undergone pancreaticoduodenectomy are not significantly different from those of healthy controls. Though the sample size of this study is small, results suggest that no change to apixaban dose regimen is needed in patients who have had a pancreaticoduodenectomy.