| 1. |
- Romeo, Alessandro, 1961, et al.
(författare)
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A wavelet add-on code for new-generation N-body simulations and data de-noising (JOFILUREN)
- 2004
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 354:4, s. 1208-1222
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Tidskriftsartikel (refereegranskat)abstract
- Wavelets are a new and powerful mathematical tool, whose most celebrated applications are data compression and de‐noising. In a previous paper, we have shown that wavelets can be used for removing noise efficiently from cosmological, galaxy and plasma N‐body simulations. The expected two‐orders‐of‐magnitude higher performance means, in terms of the well‐known Moore's law, an advance of more than one decade in the future. In this paper, we describe a wavelet add‐on code designed for such an application. Our code can be included in common grid‐based N‐body codes, is written in fortran, is portable and is available on request from the first author. The code can also be applied for removing noise from standard data, such as signals and images.
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| 2. |
- Rekić, Dinko, 1984, et al.
(författare)
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In silico prediction of efavirenz and rifampicin drug-drug interaction considering weight and CYP2B6 phenotype
- 2011
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 71:4, s. 536-43
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To test whether a pharmacokinetic simulation model could extrapolate non-clinical drug data to predict human efavirenz exposure after single and continuous dosing as well as the effects of concomitant rifampicin and further to evaluate the weight based dosage recommendations used to counteract the rifampicin-efavirenz interaction. Methods: Efavirenz pharmacokinetics were simulated using a physiologically-based pharmacokinetic model implemented in the Simcyp population-based simulator. Physicochemical and metabolism data obtained from the literature were used as input for prediction of pharmacokinetic parameters. The model was used to simulate the effects of rifampicin on efavirenz pharmacokinetics in 400 virtual patients, taking into account bodyweight and CYP2B6 phenotype. Results: Apart from the absorption phase, the simulation model predicted efavirenz concentration-time profiles reasonably well with close agreement with clinical data. The simulated effects of rifampicin co-administration on efavirenz treatment showed only a minor decrease of 16% (95%CI 13; 19) in efavirenz area under the concentration-time curve (AUC), in magnitude with what has been clinically observed (22%). Efavirenz exposure depended on CYP2B6 phenotype and bodyweight. Increasing the efavirenz dose during concomitant rifampicin was predicted to be most successful in patients over 50 kg regardless of CYP2B6 status. Conclusion: Our findings, although based on a simulation approach using limited in vitro data, support the current recommendations for using a 50 kg bodyweight cut-off for efavirenz dose increment when co-treating with rifampicin.
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| 3. |
- Henrohn, Dan, et al.
(författare)
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Acute haemodynamic response in relation to plasma vardenafil concentrations in patients with pulmonary hypertension
- 2012
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley-Blackwell. - 0306-5251 .- 1365-2125. ; 74:6, s. 990-998
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Tidskriftsartikel (refereegranskat)abstract
- AIMS To evaluate the acute haemodynamic effects of a single oral dose of vardenafil and to study the drug concentration in relation to haemodynamic effects in patients with pulmonary hypertension (PH). METHODS Sixteen patients with PH (aged 29-85\ years), received one single oral dose of vardenafil (5, 10 or 20 mg). The haemodynamic effect was assessed over a 60 min period. Vardenafil plasma concentrations were measured after 15, 30, 45 and 60 min using liquid chromatography-tandem mass spectrometry. RESULTS At 60 min a reduction in mPAP with a median % decrease of -20.3% (range -48.3 to 3.0; P < 0.001) and an increase in cardiac output and the cardiac index with a median % change of 10.6% (range -25.0 to 88.1; P = 0.015) and 12.1% (range -24.0 to 94.4; P = 0.01) respectively was observed. The pulmonary vascular resistance (PVR) was reduced with a median % decrease of -28.9% (range -61.5 to -5.9; P < 0.001), and pulmonary selectivity was reflected by a median percent reduction of -16.9% (range -49.0 to 16.5; P = 0.002; n = 14) in the PVR/ systemic vascular resistance ratio. There was a correlation between the plasma concentrations of vardenafil and change in mPAP (r = -0.579, P = 0.019) and between vardenafil concentrations and change in PVR (r = -0.662, P = 0.005). CONCLUSIONS Vardenafil causes rapid changes in cardiopulmonary haemodynamics and there is a correlation between plasma vardenafil drug concentration and the acute changes in mPAP as well as PVR in patients with PH.
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| 4. |
- Giunchi, Valentina, et al.
(författare)
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The environmental impact of pharmaceuticals in Italy : Integrating healthcare and eco-toxicological data to assess and potentially mitigate their diffusion to water supplies
- 2023
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Ingår i: British Journal of Clinical Pharmacology. - : John Wiley & Sons. - 0306-5251 .- 1365-2125. ; 89:7, s. 2020-2027
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Tidskriftsartikel (refereegranskat)abstract
- Pharmaceuticals can reach the environment at all stages of their lifecycle and accumulate in the ecosystem, potentially reaching toxic levels for animals and plants. In recent years, efforts have been made to map and control this hazard. Assessing country-specific environmental risks could drive regulatory actions towards eco-friendlier drug utilization and disposal practices. By starting from a list of 25 environmentally hazardous pharmaceuticals developed by Region Stockholm, we integrated eco-toxicological and 2019-2021 Italian drug utilization data to estimate the environmental impact of pharmaceuticals in Italy. We calculated the risk as the ratio between the predicted environmental concentration (PEC) and the predicted no-effect concentration (PNEC). We found a high risk for levonorgestrel, ciprofloxacin, amoxicillin, azithromycin, venlafaxine, sertraline and diclofenac and a moderate risk for ethinyloestradiol, oestradiol and clarithromycin. This analysis can be periodically performed to identify the pharmaceuticals with the highest risk for the environment and ascertain if containment measures should be implemented.
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| 5. |
- Nyberg, Joakim, et al.
(författare)
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Methods and software tools for design evaluation for population pharmacokinetics-pharmacodynamics studies
- 2015
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 79:1, s. 6-17
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Tidskriftsartikel (refereegranskat)abstract
- Population Pharmacokinetic (PK)-Pharmacodynamic (PD) (PKPD) models are increasingly used in drug development and in academic research. Hence designing efficient studies is an important task. Following the first theoretical work on optimal design for nonlinear mixed effect models, this research theme has grown rapidly. There are now several different software tools that implement an evaluation of the Fisher information matrix for population PKPD. We compared and evaluated five software tools: PFIM, PkStaMP, PopDes, PopED, and POPT. The comparisons were performed using two models: i) a simple one compartment warfarin PK model; ii) a more complex PKPD model for Pegylated-interferon (peg-interferon) with both concentration and response of viral load of hepatitis C virus (HCV) data. The results of the software were compared in terms of the standard error values of the parameters (SE) predicted from the software and the empirical SE values obtained via replicated clinical trial simulation and estimation. For the warfarin PK model and the peg-interferon PKPD model all software gave similar results. Of interest it was seen, for all software, that the simpler approximation to the Fisher information matrix, using the block diagonal matrix, provided predicted SE values that were closer to the empirical SE values than when the more complicated approximation was used (the full matrix). For most PKPD models, using any of the available software tools will provide meaningful results, avoiding cumbersome simulation and allowing design optimization.
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