biostudies-literatureIversen DBOdense UniversitetshospitalOdense University HospitalLundbeck FoundationNovo Nordisk Fonden3252-3262https://www.ebi.ac.uk/biostudies/studies/S-EPMC11602906biostudies-literatureUnknown90(12)<h4>Aim</h4>We aimed to assess if dicloxacillin/flucloxacillin reduces the therapeutic efficacy of direct oral anticoagulants (DOACs) and the underlying molecular mechanism.<h4>Methods</h4>In a randomized, crossover study, we assessed whether dicloxacillin reduces oral absorption of drugs through P-glycoprotein (P-gp) during 10 and 28 days of treatment. To study the impact of dicloxacillin/flucloxacillin on intestinal and hepatic expression of P-gp in vitro, we usd LS174T cells and 3D spheroids of primary human hepatocytes. Finally, we used nationwide Danish health registries and the UK's Clinical Practice Research Datalink to estimate hazard ratios (HRs) for the risk of stroke and systemic embolism following dicloxacillin/flucloxacillin exposure among DOAC users, using phenoxymethylpeniciBritish journal of clinical pharmacologyDicloxacillin is an inducer of intestinal P-glycoprotein but neither dicloxacillin nor flucloxacillin increases the risk of stroke/systemic embolism in direct oral anticoagulant users.PMC11602906R307‐2018‐2980NNF19OC0058275R307-2018-2980Potz OIversen DBStage TBBrosen KAbtahi SDunvald ADPottegard AErnst MTJeppesen GBJarvinen EKlungel OHammer HSNielsen FSouverein PDamkier PfalseDicloxacillin is an inducer of intestinal P-glycoprotein but neither dicloxacillin nor flucloxacillin increases the risk of stroke/systemic embolism in direct oral anticoagulant users.<h4>Aim</h4>We aimed to assess if dicloxacillin/flucloxacillin reduces the therapeutic efficacy of direct oral anticoagulants (DOACs) and the underlying molecular mechanism.<h4>Methods</h4>In a randomized, crossover study, we assessed whether dicloxacillin reduces oral absorption of drugs through P-glycoprotein (P-gp) during 10 and 28 days of treatment. To study the impact of dicloxacillin/flucloxacillin on intestinal and hepatic expression of P-gp in vitro, we usd LS174T cells and 3D spheroids of primary human hepatocytes. Finally, we used nationwide Danish health registries and the UK's Clinical Practice Research Datalink to estimate hazard ratios (HRs) for the risk of stroke and systemic embolism following dicloxacillin/flucloxacillin exposure among DOAC users, using phenoxymethylpenici2024-01-01T00:00:00Z2024 Dec2026-06-02T23:10:16.663Z2025-04-04T00:46:28.614ZS-EPMC116029063916000010.1111/bcp.16190