Chadi Abbara

Enzalutamide and analytical interferences in digoxin assays

Abstract Objective: We report two cases of elevated digoxin plasma levels in patients receiving enzalutamide. Cases reported: The first patient, an 84-year-old male treated with enzalutamide, was hospitalized due to deterioration in his general state. Atrial fibrillation was discovered and treatment with digoxin was initiated. Supratherapeutic digoxin concentrations (4 µg/L and 3.5 µg/L 3 days later) led to treatment being stopped despite the lack of clinical or biological signs of overdose. The second patient, an 84-year-old male treated with digoxin and enzalutamide, was hospitalized for the same reasons. Digoxin concentration upon admission was 2.8 μg/L. Despite stopping treatment, digoxin blood levels were observed to have increased on D3 and D7 following admission (3 and 3.6 μg/L, respectively). However, no clinical or biological findings indicated an overdose. Blood samples were sent to the Pharmacology and Toxicology Laboratory for analysis. Methods: The second patient’s digoxin plasma level was determined using the chemiluminescent microparticle immunoassay (CMIA®, Abbott, Illinois) method. Enzalutamide levels were determined using HPLC-UV/DAD method. An interference study was performed using different assay methods by adding enzalutamide to control plasma at various concentrations from a Xtandi® (40mg) capsule. Results: Plasma concentration of digoxin at D7 for patient 2 was identical in both laboratories (3.5 vs. 3.6 µg/L). Enzalutamide was found in the patient’s plasma (12,5 mg/L). Adding 4, 10, 20, and 40 mg/L of enzalutamide to the untreated plasma showed that the plasma concentration of digoxin was positive (from 0.35 to 3.69 µg/L) using the CMIA method. Conclusions: Our results highlight the analytical interferences of enzalutamide with digoxin assays using the CMIA method.

Analyses toxicologiques réalisées en urgence: Focus sur les indications et les méthodes analytiques utilisées dans un laboratoire hospitalier

Resume La prise en charge d’une intoxication repose avant tout sur l’anamnese et sur l’identification d’un toxidrome a partir de l’evaluation clinique et biologique. Les analyses toxicologiques peuvent completer l’evaluation clinico-biologique. La Societe de toxicologie clinique (STC) a propose une liste restreinte de molecules pouvant etre dosees en urgence dans le sang, pour lesquelles une relation effet-concentration a ete decrite en lien avec le pronostic. Les techniques de depistage sont realisees en premiere intention par immunochimie et permettent de detecter la presence de molecules ou famille de molecules. Ces techniques ont l’avantage d’etre rapides mais leurs performances analytiques doivent etre considerees en fonction de leur sensibilite et de leur specificite (possibles reactions croisees). Les resultats obtenus en depistage sont generalement verifies par des techniques plus specifiques comme la chromatographie couplee a la spectrometrie de masse qui permet d’identifier et de quantifier precisement les molecules. Aujourd’hui, de nouvelles molecules apparaissent quotidiennement sur le « marche », avec une accessibilite simplifiee sur Internet. L’identification et la quantification de ces nouvelles molecules constituent un nouveau defi pour les laboratoires.