European journal of clinical pharmacology
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Eur. J. Clin. Pharmacol. · Mar 2019
Do clinical and laboratory parameters predict thiopurine metabolism and clinical outcome in patients with inflammatory bowel diseases?
The thiopurines azathioprine and 6-mercaptopurine are frequently used for remission maintenance in patients with inflammatory bowel diseases. However, there are therapy failures, and it is unclear whether clinical and laboratory parameters can be used to predict thiopurine metabolite concentrations (as a surrogate for adequate remission maintenance therapy) and clinical outcome in these patients. ⋯ Although the models are not yet accurate enough to be used in clinical routine, model-based prediction of thiopurine metabolite concentrations and of outcome is feasible. Until more accurate models are developed and validated, traditional therapeutic drug monitoring of thiopurine metabolites in patients with inflammatory bowel diseases under thiopurine therapy stays the best tool to individualize therapy.
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Eur. J. Clin. Pharmacol. · Jan 2019
Observational StudyDose reduction, oral application, and order of intake to preserve aspirin antiplatelet effects in dipyrone co-medicated chronic artery disease patients.
Dipyrone comedication in aspirin-treated patients is associated with impaired pharmacodynamic response to aspirin (high on-treatment platelet reactivity [HTPR]). Additionally, in small observational studies, an association with impaired outcome has been described. In this uncontrolled, hypothesis-generating study, we aimed to investigate strategies to prevent this drug-drug interaction in patients with coronary artery disease (CAD). ⋯ This study shows that dipyrone should be used with caution in aspirin-treated patients. If dipyrone seems indispensable, the lowest effective dose and a strict order of intake seem favorable.
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Eur. J. Clin. Pharmacol. · Jan 2019
Presentations to the emergency department with non-medical use of benzodiazepines and Z-drugs: profiling and relation to sales data.
Non-medical use of benzodiazepines and Z-drugs is common; however, there is limited information available on the extent of harm related to this in Europe, as well as the relationship between misuse and availability. ⋯ Presentations to the emergency department associated with the non-medical use of benzodiazepines and/or Z-drugs are common, with variation in the benzodiazepines and/or Z-drugs between countries. There was a moderate to high correlation with sales data, with higher correlation in countries with higher ED presentation rates. However, this is not the only explanation for the variation in non-medical use and in the harm associated with the non-medical use of benzodiazepines/Z-drugs.
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Eur. J. Clin. Pharmacol. · Dec 2018
Pharmacodynamics and arteriovenous difference of intravenous naloxone in healthy volunteers exposed to remifentanil.
Pharmacodynamic studies of naloxone require opioid agonism. Steady state condition may be achieved by remifentanil TCI (target controlled infusion). Opioid agonism can be measured by pupillometry. It is not known whether there are arteriovenous concentration differences for naloxone. The aim was thus to further develop a model for studying pharmacokinetic/pharmacodynamic aspects of naloxone and to explore whether a significant arteriovenous concentration difference for naloxone in humans was present. ⋯ Onset of reversal by IV naloxone was rapid and lasted 118 min. The minimum effective concentration was 0.5 ng/ml. Using TCI remifentanil to obtain a steady-state opioid agonism may be a useful tool to compare new naloxone products.
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Eur. J. Clin. Pharmacol. · Dec 2018
Simulation-based suggestions to improve ibuprofen dosing for patent ductus arteriosus in preterm newborns.
Ibuprofen is the drug of choice for treatment of patent ductus arteriosus (PDA). There is accumulating evidence that current ibuprofen-dosing regimens for PDA treatment are inadequate. We aimed to propose an improved dosing regimen, based on all current knowledge. ⋯ We propose to improve intermittent ibuprofen-dosing regimens by starting with a high first dose followed by a twice-daily maintenance dosing regimen that requires increase over time and should be continued until sufficient effect has been achieved.