Clin Pharmacokinet
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Randomized Controlled Trial
Population pharmacodynamic modelling of aspirin- and Ibuprofen-induced inhibition of platelet aggregation in healthy subjects.
The objective of this study was to develop a mechanism-based pharmacodynamic model that characterizes the antiplatelet effects of aspirin (acetylsalicylic acid) and ibuprofen alone and in combination. ⋯ A mechanism-based pharmacodynamic model has been developed that characterizes the antiplatelet effects of aspirin and ibuprofen, alone and concomitantly, and predicts a significant inhibition of aspirin antiplatelet effects in the presence of a typical ibuprofen dosing regimen.
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Coumarin derivatives, including warfarin, acenocoumarol and phenprocoumon, are the drugs of choice for long-term treatment and prevention of thromboembolic events. The management of oral anticoagulation is challenging because of a large variability in the dose-response relationship, which is in part caused by genetic polymorphisms. The narrow therapeutic range may result in bleeding complications or recurrent thrombosis, especially during the initial phase of treatment. ⋯ Genetic polymorphism in further enzymes and structures involved in the effect of anticoagulants such as gamma-glutamylcarboxylase, glutathione S-transferase A1, microsomal epoxide hydrolase and apolipoprotein E appear to be of negligible importance. Despite the clear effects of CYP2C9 and VKORC1 variants, these polymorphisms explain less than half of the interindividual variability in the dose response to oral anticoagulants. Thus, while individuals at the extremes of the dose requirements are likely to benefit, the overall clinical merits of a genotype-adapted anticoagulant treatment regimen in the entire patient populations remain to be determined in further prospective clinical studies.
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Review Comparative Study
Clinical pharmacokinetics and pharmacodynamics of desloratadine, fexofenadine and levocetirizine : a comparative review.
Second-generation histamine H(1) receptor antagonists were developed to provide efficacious treatment of allergic rhinitis (AR) and chronic idiopathic urticaria (CIU) while decreasing adverse effects associated with first-generation agents. When comparing the efficacy and safety profiles of the newest second-generation antihistamines - desloratadine, fexofenadine and levocetirizine - many pharmacological and clinical criteria must be considered. Most importantly, these elements should not be evaluated separately but, rather, as parts of a puzzle that create a whole picture. ⋯ Desloratadine and fexofenadine do not impair cognitive or psychomotor functioning and are comparable with placebo in terms of somnolence. Based on these pharmacological characteristics, as well as clinical endpoints such as symptom scores, quality-of-life surveys, inflammatory cell counts and investigators' global evaluations, we conclude that desloratadine, fexofenadine and levocetirizine are all efficacious treatments for AR and CIU. However, differences among the antihistamines in relation to a lack of significant interaction with drug transporter molecules and somnolence in excess of placebo may provide some advantages for the overall profile of desloratadine compared with fexofenadine and levocetirizine.
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Controlled Clinical Trial
Population pharmacokinetics of meropenem in critically ill patients undergoing continuous renal replacement therapy.
Meropenem is a carbapenem antibacterial frequently prescribed for the treatment of severe infections in critically ill patients, including those receiving continuous renal replacement therapy (CRRT). The objective of this study was to develop a population pharmacokinetic model of meropenem in critically ill patients undergoing CRRT. ⋯ A population pharmacokinetic model of meropenem in intensive care patients undergoing CRRT was developed and validated. CL(CR) and the patient type (whether septic or polytraumatized) were identified as significant covariates. The population pharmacokinetic model developed in the present study has been employed to recommend continuous infusion protocols in patients treated with CRRT.
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Drug-drug interactions are a recurring problem in immunocompromised patients treated with triazole antifungals. While the introduction of new antifungals has expanded opportunities for lowering drug toxicity, virtually all antifungal regimens carry the risk of pharmacokinetic and pharmacodynamic interaction. This review presents the published data on molecular determinants (enzymes, transporters, orphan nuclear receptors) of systemic triazole pharmacokinetics in humans, including itraconazole, fluconazole, voriconazole and posaconazole. ⋯ In addition, some are substrates and/or inhibitors of drug transporters such as multidrug resistance-1 gene product, P-glycoprotein, or breast cancer resistance protein. The interactions of triazole antifungals can be divided into the following categories: modifications of antifungal pharmacokinetics by other drugs, modifications of other drug pharmacokinetics by antifungals, and two-way interactions. These features are the basis of most interactions that occur during triazole therapy.