1,720,990 research outputs found
A modeling tool for the personalization of pharmacokinetic predictions
No full textA method to apply pharmacokinetic models to assist physicians in therapeutic drug monitoring is proposed. The practice of therapeutic drug monitoring is required for drugs characterized by a narrow therapeutic index, which consequently present toxicity concerns. The proposed method employs a physiologically based pharmacokinetic (PBPK) model to determine an initial assessment of the pharmacokinetics (PK) of a specific patient. To further increase the precision of this prediction, the method uses two experimental datasets: (i) the PK data from a group of reference subjects, and (ii) limited drug blood concentration measures of the specific patient under study. By combining the available information, it is possible to assess the precision of the initial model prediction and determine a correction factor to improve it. The resulting patient-specific PBPK model produces encouraging results as there is a concrete reduction in prediction errors of the individualized PK with respect to experimental data
Innovations and improvements in pharmacokinetic models based on physiology
No full textBackground: Accompanied by significant improvements of modeling techniques and computational methods in medical sciences, the last thirty years saw the flourishing of pharmacokinetic models for applications in the pharmacometric field. In particular, physiologically based pharmacokinetic (PBPK) models, grounded on a mechanistic foundation, have been applied to explore a multiplicity of aspects with possible applications in patient care and new drugs development, as in the case of siRNA therapies. Method: This article summarizes the features we recently introduced in PBPK modeling within a threeyear research project funded by Italian Research Ministry. Four major points are detailed: (i) the mathematical formulation of the model, which allows modulating its complexity as a function of the administration route and active principle; (ii) a dedicated parameter of the PBPK model quantifies the drugprotein binding, which affects the active principle distribution; (iii) the gall bladder compartment and the bile enterohepatic circulation process; (iv) the coupling of the pharmacokinetic and pharmacodynamic models to produce an overall understanding of the drug effects on mammalian body. Results: The proposed model is applied to two separate endovenous (remifentanil) and oral (sorafenib) drug administrations. The resulting PBPK simulations are consistent with the literature experimental data. Blood concentration predictability is confirmed in multiple reference subjects. Furthermore, in case of sorafenib administration in mice, it is possible to evaluate the drug concentration in the liver and reproduce the effects of the enterohepatic circulation. Finally, a preliminary application of the coupling of the pharmacokinetic/pharmacodynamic models is presented and discussed
A New Filter Concept Yielding Improved Resolution and Throughput in Radiation Detection System.
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A weighted least mean squares linear algorithm for energy and occurrence time measurement of pulses
No full textThe availability of high performance configurable digital processors offers the possibility of real-time implementation
of digital least-mean-square analysis methods in nuclear
spectroscopy. A particularly simple, efficient and highly precise
technique for reducing the mathematical complexity of
least-mean-square algorithms used in deriving energy and arrival
time of detected events is presented. The method has been
theoretically developed and validated through comparison with
state-of-the-art digital signal processing techiques
Self-configuring digital processor for on-line pulse analysis
No full textAn adaptive self-calibrating instrument for digital spectroscopy is proposed and demonstrated. Most of the typical processing features (pole-zero cancellation, baseline restoration, and shaping) are digitally implemented and optimized. The main
feature of the processor is the capability to self-calibrate and selfoptimize the configurable sections of the whole measurement setup, both digital and analog parts. This is accomplished through automatic dynamic initialization procedures, which make the system particularly user friendly and flexible to varying operative conditions while keeping very high resolution performances
Segmented quasi-coaxial HP-Ge detectors optimized for spatial localization of the events
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Enterohepatic Circulation Effect in Physiologically Based Pharmacokinetic Models: The Sorafenib Case
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