Pharmacokinetic Modeling of Morphine's Effect on Plasma Concentrations of Ticagrelor and Its Metabolite in Healthy Volunteers.

This study aimed to build a mathematical model describing the pharmacokinetics of ticagrelor and its active metabolite (AR-C124910XX) in a stable setting with concomitant administration of morphine. The model consists of a set of four differential equations prepared upon the available knowledge regarding the biological processes in the pharmacokinetics of ticagrelor. The set of equations was solved numerically using the Runge-Kutta method.

Acute Limb Ischemia after Intake of the Phenylethylamine Derivate NBOMe.

: N-(2-methoxy) benzyl-phenethylamine (NBOMe) derivatives have a high affinity to the serotonin receptor 2A and emerged as new psychedelic agents. We report the case of a 30-year-old man admitted to the hospital because of acute ischemia of the left arm with clinical symptoms of pallor, pulselessness, paresthesia, and a motoric deficit. The patient had a history of schizophrenia and drug abuse and disclosed during the hospital stay the sublingual intake of a substance bought as 25I-NBOMe the night before the ischemic event.

Morphine Interaction with Aspirin: a Double-Blind, Crossover Trial in Healthy Volunteers.

Aspirin is a cornerstone in the antiplatelet therapy for acute coronary syndromes. Coadministration of morphine may potentially influence the intestinal absorption, pharmacokinetics, and pharmacodynamics, as seen with P2Y inhibitors. In this trial, healthy volunteers were randomized to receive morphine (5 mg, i.

Clopidogrel in Critically Ill Patients.

Only limited data are available regarding the treatment of critically ill patients with clopidogrel. This trial investigated the effects and the drug concentrations of the cytochrome P450 (CYP450) activated prodrug clopidogrel (n = 43) and the half-life of the similarly metabolized pantoprazole (n = 16) in critically ill patients. ADP-induced aggregometry in whole blood classified 74% (95% confidence intervals 59-87%) of critically ill patients as poor responders (n = 43), and 65% (49-79%) responded poorly according to the vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) assay.

Ticagrelor mitigates ischaemia-reperfusion induced vascular endothelial dysfunction in healthy young males - a randomized, single-blinded study.

Aims: Animal data suggest that ticagrelor but not clopidogrel protects against tissue injury. It is unclear if this effect of ticagrelor is also detectable in humans. We studied the effect of ticagrelor and clopidogrel at standard clinical doses on endothelial dysfunction in an experimental model of forearm vascular ischaemia-reperfusion (IR) injury.

Prasugrel in critically ill patients.

While prasugrel is indicated for the treatment of myocardial infarction, its effects in the most severely affected patients requiring intensive care is unknown, so that we measured the antiplatelet effects and sparse pharmacokinetics of prasugrel in critically ill patients. Twenty-three patients admitted to medical intensive care units, who were treated with 10 mg prasugrel once daily, were included in this prospective trial. Critically ill patients responded poorly to daily prasugrel treatment: adenosine diphosphate (ADP)-induced aggregation in whole blood classified 65 % (95 % confidence intervals (CI) 43-84 %) of patients as having high on treatment platelet reactivity, platelet function under high shear rates even 74 % (95 %CI 52-90 %).

Acetylsalicylic acid in critically ill patients: a cross-sectional and a randomized trial.

Background: Despite decades of clinical use, the pharmacokinetics and the effects of acetylsalicylic acid (ASA) in critically ill patients remain ill-defined. We aimed to investigate the pharmacokinetics and the effects of different ASA formulations during critical illness.

Design: A cross-sectional study and a randomized, parallel-group trial were performed.

Abciximab as a bridging strategy to overcome morphine-prasugrel interaction in STEMI patients.

Objective: The present study investigated whether the glycoprotein (GP)IIb/IIIa receptor blocker abciximab might be a successful bridging strategy to achieve adequate levels of platelet inhibition rapidly in cases where prasugrel is used in morphine-pretreated ST-elevation myocardial infarction (STEMI) patients.

Methods: In a prospective observational cohort study, 32 patients presenting with STEMI were given prasugrel at a loading dose of 60 mg. Patients were stratified into four groups, according to morphine and/or abciximab use.

Potent irreversible P2Y12 inhibition does not reduce LPS-induced coagulation activation in a randomized, double-blind, placebo-controlled trial.

Platelets play an important role in the activation of coagulation. P2Y12 receptor inhibition may be beneficial in inflammatory states. Prasugrel, a potent irreversible inhibitor of P2Y12 receptor-induced platelet activation may reduce activation of coagulation in a human LPS (lipopolysaccharide) model.

Morphine interaction with prasugrel: a double-blind, cross-over trial in healthy volunteers.

Background: Morphine decreases the concentrations and effects of clopidogrel, which could lead to treatment failure in myocardial infarction.

Objectives: To clarify whether more potent P2Y12-inhibitors may provide an effective alternative, we examined drug-drug interactions between morphine and prasugrel.

Methods: Twelve healthy volunteers received 60 mg prasugrel with placebo or 5 mg morphine intravenously in a randomized, double-blind, placebo-controlled, cross-over trial.

Morphine decreases ticagrelor concentrations but not its antiplatelet effects: a randomized trial in healthy volunteers.

Background: Our recent drug interaction trial with clopidogrel shows that morphine decreases the concentrations and pharmacodynamic effects of clopidogrel, which could lead to treatment failure in susceptible individuals. We hypothesized that the pharmacodynamic consequences of drug-drug interactions would be less between morphine and ticagrelor.

Materials And Methods: Twenty-four healthy subjects received a loading dose of 180 mg ticagrelor together with placebo or 5 mg morphine intravenously in a randomized, double-blind, placebo-controlled, crossover trial.

Absorption kinetics of low-dose chewable aspirin--implications for acute coronary syndromes.

Background: This study describes the implications of the pharmacokinetics of low-dose chewable aspirin for acute coronary syndromes. Current guidelines recommend the administration of 162-325 mg aspirin chewing tablets for the treatment of acute myocardial infarction. Although aspirin is widely used and a cornerstone in myocardial infarction, there is no information available on the pharmacokinetics of low doses of chewable aspirin.

Morphine decreases clopidogrel concentrations and effects: a randomized, double-blind, placebo-controlled trial.

Objectives: This study sought to examine the possible drug-drug interactions between clopidogrel and morphine.

Background: Because morphine-the recommended treatment for pain of myocardial infarction-is associated with poor clinical outcome, we hypothesized that morphine lowers the plasma levels of clopidogrel active metabolite as well as its effects on platelets.

Methods: Twenty-four healthy subjects received a loading dose of 600 mg clopidogrel together with placebo or 5 mg morphine intravenously in a randomized, double-blind, placebo-controlled, cross-over trial.

Reversal strategy in antagonizing the P2Y12 -inhibitor ticagrelor.

Background: Patients on antiplatelet therapy have a higher incidence of bleeding complications. Reversal of antiplatelet drug effects is an important issue at trauma or emergency departments. For old and conventional anticoagulants, reversal strategies are established.

Comparison of a new ELISA-based with the flow cytometric assay for vasodilator-associated stimulated phosphoprotein phosphorylation to assess P2Y12 -inhibition after ticagrelor intake.

Background: Ticagrelor is a P2Y12 receptor antagonist, with superior effects but also ensuing enhanced bleeding risk as compared to clopidogrel. Determination of platelet inhibition may be useful to confirm efficient platelet inhibition on an individual patient level and to identify patients at risk for bleeding. The vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation assay specifically measures platelet P2Y12 inhibition, but has so far required individual sample processing.

Comparison of a new ELISA-based with the flow cytometric assay for vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation to assess P2Y -inhibition after ticagrelor intake.

Background: Ticagrelor is a P2Y receptor antagonist, with superior effects but also ensuing enhanced bleeding risk as compared to clopidogrel. Determination of platelet inhibition may be useful to confirm efficient platelet inhibition on an individual patient level and to identify patients at risk for bleeding. The vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation assay specifically measures platelet P2Y inhibition, but has so far required individual sample processing.

Simultaneous determination of acetylsalicylic acid and salicylic acid in human plasma by isocratic high-pressure liquid chromatography with post-column hydrolysis and fluorescence detection.

A selective, sensitive and rapid high-performance liquid chromatography method with post-column hydrolysis and fluorescence detection was developed for the simultaneous quantification of acetylsalicylic acid and its metabolite salicylic acid in human plasma. Following the addition of 2-hydroxy-3-methoxybenzoic acid as internal standard and simple protein precipitation with acetonitrile, the analytes were separated on a ProntoSIL 120 C18 ace-EPS column (150 × 2 mm, 3 µm) protected by a C8 guard column (5 µm). The mobile phase, 10 mm formic acid in water (pH 2.

A randomized, double-blind, parallel, single-site pilot trial to compare two different starting doses of methotrexate in methotrexate-naïve adult patients with rheumatoid arthritis.

Background: Methotrexate (MTX) is a cornerstone in the treatment of rheumatoid arthritis. Despite its widespread use, expert opinions differ about the optimal MTX starting dosage to achieve rapid onset of action while averting increased occurrence of adverse effects. Plasma concentrations have not been assessed in previous studies that monitored clinical efficacy.

A short-chain methotrexate polyglutamate as outcome parameter in rheumatoid arthritis patients receiving methotrexate.

Objectives: Methotrexate (MTX) is a cornerstone in the treatment of rheumatoid arthritis (RA). Although in general MTX is very effective, the major drawback is the large inter-patient variability in clinical response. The circulating levels of MTX polyglutamates (MTXPGs) are supposed to correlate with clinical efficacy, therefore having a potential role in drug monitoring.

The influence of methotrexate on the gene expression of the pro-inflammatory cytokine IL-12A in the therapy of rheumatoid arthritis.

Objectives: Methotrexate (MTX) is a cornerstone in the treatment of rheumatoid arthritis (RA). Among its anti-proliferative activity, the anti-inflammatory mechanisms of MTX seem to play a major role in the treatment of RA. MTX reduces the production of pro-inflammatory cytokines such as interleukin (IL)-1, IL-2, IL-6 and interferon (INF)-γ, while the gene expression of anti-inflammatory Th2 cytokines like IL-4 and IL-10 is increased - altogether resulting in the anti-inflammatory effect.