Does morphine administration affect ticagrelor conversion to its active metabolite in patients with acute myocardial infarction? A sub-analysis of the randomized, double-blind, placebo- -controlled IMPRESSION trial

Background. Therapy with aspirin and one of the platelet P2Y12 receptor inhibitors, preferably ticagrelor or prasugrel, is the mainstay of acute myocardial infarction (AMI) treatment. Morphine is the most commonly used analgesic in AMI patients. The IMPRESSION study was the first randomized trial to confirm that morphine use in this clinical setting leads to a delayed and attenuated exposure to ticagrelor and its active metabolite (AR-C124910XX). The mechanism underlying this drug-drug interaction remains hypothetical. Material and methods. A post hoc sub-analysis of the IMPRESSION study, a phase IV, single center, randomized, double-blind, placebo-controlled trial, was performed to examine whether morphine administration interferes with the proportion of AR-C124910XX produced from ticagrelor in AMI patients. Pharmacokinetic results of all subjects pretreated with placebo (n = 35) and morphine (n = 35) were analyzed. The ratio of total exposure to AR-C124910XX to total exposure to ticagrelor for 12 h was used to illustrate the rate of ticagrelor metabolism. Total exposure to investigated compounds was measured as the area under the plasma concentration-time curve (AUC). Results. The ratios of AUC(0–12) for AR-C124910XX to AUC(0–12) for ticagrelor were comparable between morphine and placebo pretreated patients (20.9 [13.9–34.6] v. 24.7 [18.1–29.6] %; p = 0.58). Importantly, visual inspection of the relationship between AUC(0–12) for AR-C124910XX and AUC(0–12) for ticagrelor revealed that regression lines for the morphine and placebo groups were located closely to each other, with a tendency for superimposing. Additionally, we observed similar values of slope coefficients for both study arms in the linear regression equations illustrating the relationship between AUC(0–12) for AR-C124910XX and AUC(0–12) for ticagrelor (0.19 [± 0.03] v. 0.21 [± 0.04]; p for the statistical significance of both slope coefficients < 0.0001). Conclusions. In the IMPRESSION study, conversion of ticagrelor to AR-C124910XX in AMI patients was not affected by morphine administration

Ligand fishing using new chitosan based functionalized AndrogenReceptor magnetic particles

Superparamagnetic nanoparticles with chemically modified chitosan has been proposed as a potentialsupport for the immobilization of the androgen receptor (AR). The study involved comparison of differentAR carriers like commercially available magnetic beads coated with silica (BcMag) and chitosan coatednanoparticles with different amount of amino groups. The immobilization was carried out through cova-lent immobilization of the AR through the terminal amino group or through available carboxylic acids.The initial characterization of the AR coated magnetic beads was carried out with dihydrotestosterone,a known AR ligand. Subsequently, chitosan modified nanporticles with long-distanced primary aminogroups (Fe3O4CS-(NH2)3) (upto 8.34 mM/g) were used for further study to isolate known AR ligands(bicalutamide, flutamide, hydroxyflutamide and levonogestrel) from a mixture of tested compounds inammonium acetate buffer [10 mM, pH 7.4]. The results showed that the selected nanoparticles are apromising semi-quantitative tool for the identification of high affinity compounds to AR and might be ofspecial importance in the identification of novel agonists or antiandrogens