In-Vitro Sorbent-Mediated Removal of Edoxaban from Human Plasma and Albumin Solution

BACKGROUND AND OBJECTIVE: Based on previous experience of sorbent-mediated ticagrelor, dabigatran, and radiocontrast agent removal, we set out in this study to test the effect of two sorbents on the removal of edoxaban, a factor Xa antagonist direct oral anticoagulant. METHODS: We circulated 100 mL of edoxaban solution during six first-pass cycles through 40-mL sorbent columns (containing either CytoSorb in three passes or Porapak Q 50-80 mesh in the remaining three passes) during experiments using human plasma and 4% bovine serum albumin solution as drug vehicles. Drug concentration was measured by liquid chromatography-tandem mass spectrometry. RESULTS: Edoxaban concentration in two experiments performed with human plasma dropped from 276.8 to 2.7 ng/mL and undetectable concentrations, respectively, with CytoSorb or Porapak Q 50-80 mesh (p = 0.0031). The average edoxaban concentration decreased from 407 ng/mL +/- 216 ng/mL to 3.3 ng/mL +/- 7 ng/mL (p = 0.017), for a removal rate of 99% across all six samples of human plasma (two samples) and bovine serum albumin solution (four samples). In four out of the six adsorbed samples, the drug concentrations were undetectable. CONCLUSION: Sorbent-mediated technology may represent a viable pathway for edoxaban removal from human plasma or albumin solution

Experimental first-pass method for testing and comparing sorbent polymers used in the clearance of iodine contrast materials

Background: Sorbents have been shown to adsorb iodinated radiocontrast media. Objective: In this study we describe a simple method to compare various sorbents in terms of capacity to adsorb radiocontrast media. Methods: Iodixanol solution was injected into columns filled with three types of sorbent at filtration velocities of increasing magnitude. Two variables of interest – contrast removal rate and matched iodine retention (MIR) – were calculated to measure the adsorption efficiency and the mass of contrast iodine adsorbed versus sorbent used, respectively. Results: The highest contrast removal and MIR for Porapak Q, CST 401 and Amberlite XAD4 were 41, 38 and 16% (p = 0.22 and 0.0005 for comparisons between Porapak Q-CST 401 and CST 401-Amberlite XAD4) and 0.060, 0.055 and 0.024, respectively (p = 0.18 and 0.0008). Extrapolation to a clinical scenario may suggest that removal of 8 ml iodixanol could be achieved by masses of sorbents of 43, 47 and 107 g, respectively. Conclusion: In this study we set a benchmark for comparing the radiocontrast-adsorbing efficiency of polymer sorbents during first-pass experiments, using a readily available methodology

Ticagrelor Removal From Human Blood

Summary: The authors devised an efficient method for ticagrelor removal from blood using sorbent hemadsorption. Ticagrelor removal was measured in 2 sets of in vitro experiments. The first set was a first-pass experiment using bovine serum albumin (BSA) solution pre-incubated with ticagrelor, whereas the second set, performed in a recirculating manner, used human blood mixed with ticagrelor. Removal of ticagrelor from BSA solution reached values >99%. The peak removal rate was 99% and 94% from whole blood and 99.99% and 90% from plasma during 10 h and 3 to 4 h of recirculating experiments, respectively. In conclusion, hemadsorption robustly removes ticagrelor from BSA solution and human blood samples. Key Words: concentration, drug, P2Y12, platelet, removal, sorbent, ticagrelo

Detection of morphological markers of vulnerable atherosclerotic plaque using multimodal spectroscopy

Vulnerable plaques, which are responsible for most acute ischemic events, are presently invisible to x-ray angiography. Their primary morphological features include a thin or ulcerated fibrous cap, a large necrotic core, superficial foam cells, and intraplaque hemorrhage. We present evidence that multimodal spectroscopy (MMS), a novel method that combines diffuse reflectance spectroscopy (DRS), intrinsic fluorescence spectroscopy (IFS), and Raman spectroscopy (RS), can detect these markers of plaque vulnerability. To test this concept, we perform an MMS feasibility study on 17 human carotid artery specimens. Following the acquisition of spectra, each specimen is histologically evaluated. Two parameters from DRS, hemoglobin concentration and a scattering parameter, are used to detect intraplaque hemorrhage and foam cells; an IFS parameter that relates to the amount of collagen in the topmost layers of the tissue is used to detect the presence of a thin fibrous cap; and an RS parameter related to the amount of cholesterol and necrotic material is used to detect necrotic core. Taken together, these spectral parameters can generally identify the vulnerable plaques. The results indicate that MMS provides depth-sensitive and complementary morphological information about plaque composition. A prospective in vivo study will be conducted to validate these findings.National Institutes of Health (U.S.) (Grant R01-HL-64675)National Institutes of Health (U.S.) (Grant P41-RR-02594