Open AccessInfluence of proton pump inhibitors on blood dabigatran concentrations in Japanese patients with non‐valvular atrial fibrillation
Author(s) -
Kuwayama Tasuku,
Osanai Hiroyuki,
Ajioka Masayoshi,
Tokuda Kotaro,
Ohashi Hirofumi,
Tobe Akihiro,
Yoshida Tatsuya,
Masutomi Tomohiro,
Kambara Takahiro,
Inoue Yosuke,
Nakashima Yoshihito,
Asano Hiroshi,
Sakai Kazuyoshi
Publication year - 2017
Publication title -
journal of arrhythmia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.463
H-Index - 21
eISSN - 1883-2148
pISSN - 1880-4276
DOI - 10.1016/j.joa.2017.07.013
Subject(s) - dabigatran , medicine , atrial fibrillation , direct thrombin inhibitor , proton pump inhibitor , drug , cardiology , anesthesia , pharmacology , warfarin
Background Dabigatran is a direct thrombin inhibitor used to decrease the risk of ischemic stroke in patients with non‐valvular atrial fibrillation (NVAF). Its prodrug, dabigatran etexilate (DE) is often co‐administrated with a proton pump inhibitor (PPI) because of its adverse effects on the gastrointestinal tract. Drug‐drug interactions between DE and PPIs in daily clinical practice have not been fully elucidated. Methods Changes in blood dabigatran concentration (DC) were investigated using the dilute thrombin time test in a randomized, open‐label, two‐period crossover study including 34 Japanese patients with NVAF receiving dabigatran therapy with or without PPI. Results The average trough DC was significantly higher without PPI than with PPI (83 ± 42.3 vs. 55.5 ± 24.6 ng/mL, respectively; P < 0.001). Similarly, the average peak DC was significantly higher without PPI than with PPI (184.1 ± 107.7 vs. 124 ± 59.2 ng/mL, respectively; P = 0.0029). The average ratio of DC change at the trough and peak levels did not differ significantly among the three PPI types. Conclusions PPI administration significantly decreased the trough and peak DCs in patients with NVAF. Therefore, when prescribing PPIs for patients with NVAF in a clinical setting, the possibility that the bioavailability of dabigatran may decrease should be considered.