European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
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For about 15 years the performance of dry powder inhalers (DPIs) has been numerically analysed through CFD (computational fluid dynamics) approaches with the objective of understanding the evolving flow structures and the resulting transport of drug particles. Naturally the main interest is the numerical prediction of the emitted fine particle fraction (FPF) which is able to penetrate the lung airways. Due to the mostly used drug formulations (i.e. carrier-based or agglomerated drug powder) and the complex elementary processes occurring during the transport of such particles through inhalers this is not an easy task. ⋯ Hence, the predicted fine particle fraction was found to be close to 100% for both inhalers. As a conclusion of this study, it has become clear that the wall deposition of fine drug particles is an important mechanism during carrier or agglomerate wall collisions, which are responsible for the low emitted fine particle fraction (FPF) observed experimentally. It is hoped that this article provides requirements and guidelines for the further development of Euler/Lagrange simulations applied to dry powder inhaler devices.
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Pain is a complex biopsychosocial phenomenon of which the intensity, location and duration depends on various underlying components. Treatment of pain is associated with considerable inter-individual variability, and as such, requires a personalized approach. However, a priori prediction of optimal analgesic treatment for individual patients is still challenging. ⋯ Moreover, combination of QSP modelling with state-of-the-art metabolomics approaches may offer unique possibilities to identify novel pain biomarkers. Such biomarkers could support both the personalized treatment of pain and translational drug development of novel analgesic agents. In conclusion, a QSP approach will likely improve our ability to predict pain and treatment response, paving the way for personalized treatment of pain.
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Morphine is a widely used opioid for treatment of moderate to severe pain, but large interindividual variability in patient response and no clear guidance on how to optimise morphine dosage regimen complicates treatment strategy for clinicians. Population pharmacokinetic-pharmacodynamic models can be used to quantify dose-response relationships for the population as well as interindividual and interoccasion variability. Additionally, relevant covariates for population subgroups that deviate from the typical population can be identified and help clinicians in dose optimisation. ⋯ Furthermore, based on simulations from key pharmacokinetic-pharmacodynamic models, the contribution of morphine-6-glucuronide to the analgesic response in patients with renal insufficiency was investigated. Simulations were also used to examine the impact of effect-site equilibration half-life on time course of response. Lastly, the impact of study design on the likelihood of determining accurate pharmacodynamic parameters for morphine response was evaluated.
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Type 2 diabetes mellitus is a major and growing health problem throughout the world. Current treatment approaches include diet, exercise, and a variety of pharmacological agents including insulin, biguanides, sulfonylureas and thiazolidinediones. New therapies are still needed to control metabolic abnormalities, and also to preserve beta-cell mass and to prevent loss of beta-cell function. ⋯ However, both the strategies are having their own advantages and limitations. The present review summarizes the concepts of GLP-1 based therapy for type 2 diabetes and the current preclinical and clinical development in GLP-1 mimetics and DPP-IV inhibitors. Further, the potential advantages and the limitations of both the strategies are discussed.
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Transporters play an important role in the processes of drug absorption, distribution and excretion. In this review, we have focused on the involvement of transporters in drug excretion in the liver and kidney. The rate of transporter-mediated uptake and efflux determines the rate of renal and hepatobiliary elimination. ⋯ More recently, some methods to analyze such transporter-mediated transport have been reported. The estimation of the contributions of transporters to the net clearance of a drug makes it possible to predict the net clearance from data involving drug transport in transporter-expressing cells. Double transfected cells, where both uptake and efflux transporters are expressed on the same polarized cells, are also helpful for the analysis of the rate of transporter-mediated transcellular transport.