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Abstract Introduction Estimation of residual apixaban plasma concentrations may be requested in the management of emergencies. This study aims at assessing the performance of specific anti‐Xa assays calibrated with apixaban on real‐life samples with low apixaban plasma concentrations (<30 ng/mL) and on‐treatment ranges, with and without interference of low‐molecular‐weight heparin (LMWH). Methods The performance of the STA ® ‐Liquid Anti‐Xa assay (STA ® LAX) and the low and normal procedures of the Biophen ® Direct Factor Xa Inhibitors (DiXaI) assay was tested on 134 blood samples, collected from patients on apixaban, wherefrom 74 patients received LMWH after apixaban cessation. The results were compared with the liquid chromatography coupled with tandem mass spectrometry (LC‐MS/MS) measurements. Results The Biophen ® DiXaI, Biophen ® DiXaI LOW, and STA ® LAX showed very good correlation with LC‐MS/MS measurements in patients without LMWH administration (Spearman r .95, .99, and .98, respectively). Their limits of quantitation were defined at 48, 24, and 12 ng/mL, respectively. The Bland‐Altman test measured mean bias (SD) at 5.6 (13.1), −2.5 (5.0), and −0.8 (6.1) ng/ml, respectively. The Spearman r of the Biophen ® DiXaI decreased to 0.64 in presence of low apixaban concentrations. The Spearman r of the Biophen ® DiXaI LOW and STA ® LAX decreased to 0.39 and 0.26, respectively, in presence of LMWH. Conclusions The accuracy of the low methodologies (Biophen ® DiXaI LOW and STA ® LAX) is slightly improved for low apixaban plasma concentrations, compared with the normal procedure of Biophen ® DiXaI. The interference of LMWH on the low methodologies is measurable, however, less important than the previously reported interference of LMWH on rivaroxaban calibrated specific anti‐Xa assays.
BackgroundIn lung transplant patients, direct oral anticoagulants are often taken in combination with immunosuppressive drugs such as tacrolimus. Since tacrolimus is a substrate and inhibitor of the efflux protein ABCB1, also transporting direct oral anticoagulants, a possible drug–drug interaction mediated by competition for this transporter needs to be investigated.ObjectivesTo determine the in vitro effect of tacrolimus on ABCB1-mediated rivaroxaban transport in order to support clinician practice.MethodsRecombinant cell line models, based on human embryonic kidney 293 cells, were generated by a stable transfection process to overexpress ABCB1 or not (control cells). The impact of tacrolimus on ABCB1-mediated rivaroxaban transport was assessed by accumulation experiments.ResultsABCB1 expression decreased the cellular accumulation of rivaroxaban and tacrolimus at their respective clinically relevant concentrations when compared with control cells. This confirms the involvement of ABCB1 in the active transport of tacrolimus and rivaroxaban. However, tacrolimus had no significant influence on rivaroxaban disposition at those clinically relevant concentrations.ConclusionOur study does not provide evidence for a possible interaction between tacrolimus and rivaroxaban when used together in practice.
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