The saturation of these transporters might explain the increase in the Apixaban concentration due to a diminution of its efflux. ABCB1 and ABCG2 are both intestinal efflux transporters that may be involved in the enteroenteric recirculation of Apixaban observed in animal studies 9. Indeed, Apixaban is mainly metabolized by cytochrome P450 family 3 subfamily A member 4 ( CYP3A4/ 5) and is a substrate of P‐glycoprotein ( ABCB1) and Breast Cancer Resistance Protein ( ABCG2) 8. Another hypothesis would be a saturation of the intestinal cytochromes and transporters or metabolism by the high amount of Apixaban and other medication. This can be explained by the high number of tablets ingested (~100) which could have formed an agglomeration of pills and limited the dissolution of the tablets and prolonged absorption of the drug. As previously described, a delayed absorption was observed with a Tmax at 17 h, about four times the usual Tmax value (median : 4 h ) 4. Apixaban absorption is usually described as linear up to 10 mg and non‐linear beyond, with clearly decreased dissolution, absorption and bioavailability at doses higher than 25 mg 2. The apparent half‐life is close to the usual value at therapeutic doses (mean/SD: 11.7 h/3.3) 4. This is the fourth published case of self‐poisoning with Apixaban 5, 6, 7, with the highest concentrations reported so far. Another important finding is that anti‐Xa activity seems to be linearly related to concentrations up to 4000 μg l −1. In this clinical case of Apixaban intoxication, we found concentrations approximately 28‐fold higher than therapeutic concentrations, a largely delayed Tmax but a normal elimination half‐life. However, the diagnosis was excluded by the D‐dimer results (below the cut‐off level of 680 μg l −1) which were 448 μg l −1 when PE was suspected and 424 μg l −1 7 days later. Ironically, Apixaban was reintroduced 6 days later as the patient had a suspected pulmonary embolism (PE) based on clinical signs (chest pains and breathlessness). The patient remained under medical supervision for 2 days and was then transferred to the psychiatric. Three measurements were performed during hospitalization, at 16.8, 39.7 and 70.8 h after the intake leading to plasma concentrations, estimated using the anti‐Xa activity, of 2703, 570 and 109 μg l −1, respectively. As Apixaban exposure is closely correlated to the anti‐Xa activity, the drug measurement of Apixaban is not performed 24 h/24 h in our laboratory. Indeed, it has been shown that activated charcoal administered between 2 to 6 h after intake reduces the area under the curve and half‐life at therapeutic doses 2, 3. Activated charcoal was not used because more than 6 h had passed since the drug intake. N‐acetylcysteine was initiated to prevent hepatic injury while no other medication was initiated. The first toxicological tests, carried out on admission, revealed an undetectable alcohol blood concentration and an acetaminophen plasma concentration at 86.3 mg l −1 (therapeutic trough concentrations between 5 and 25 mg l −1). The clinical examination did not show any organ dysfunctions or haemorrhagic signs, and the patient's life was not in danger. Upon admission, the patient explained that 5 h earlier, he had taken 60 tablets of Apixaban, 16 g of Acetaminophen, approximatively 10 tablets of Oxazepam and a few other drugs (not specified). His medical history included a heart attack and high blood pressure treated by beta‐blockers (bisoprolol), anticoagulant (Apixaban), antianginal drugs (Nitroglycerin and Nicorandil), diuretic (Furosemide) and statins, diabetes treated by insulin and a severe depression treated by antidepressants (Vortioxetine) and anxiolytic benzodiazepine (Oxazepam). A 67‐year‐old man with a medical history of depression was admitted to the emergency department after deliberate self‐poisoning.
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