tPharmacokinetic modeling based on a mechanistic approach is a promising tool for drug concentrationprediction in living beings. The development of a reduced physiologically-based pharmacokinetic model(PBPK model), is performed by lumping organs and tissues with comparable characteristics respect todrug distribution phenomena. The proposed reduced model comprises eight differential equations and18 adaptive parameters. To improve the quality of the PBPK model these adaptive parameters are alterna-tively: (i) individualized according to literature correlations on the physiological features of each patient;(ii) assigned as constants based on the features of either human body or drug properties; (iii) regressedrespect to experimental data.The model predictive capability is validated with experimental blood concentrations of remifentanil,an analgesic drug, administered via bolus injection with four doses (2, 5, 15, 30 g/kg) to mixed groupsof patients. Concentration profiles for the four simulated doses reveal a rather good consistency withexperimental data.

Definition and validation of a patient-individualized physiologically-based pharmacokinetic model

GRASSI, Mario;
2016

Abstract

tPharmacokinetic modeling based on a mechanistic approach is a promising tool for drug concentrationprediction in living beings. The development of a reduced physiologically-based pharmacokinetic model(PBPK model), is performed by lumping organs and tissues with comparable characteristics respect todrug distribution phenomena. The proposed reduced model comprises eight differential equations and18 adaptive parameters. To improve the quality of the PBPK model these adaptive parameters are alterna-tively: (i) individualized according to literature correlations on the physiological features of each patient;(ii) assigned as constants based on the features of either human body or drug properties; (iii) regressedrespect to experimental data.The model predictive capability is validated with experimental blood concentrations of remifentanil,an analgesic drug, administered via bolus injection with four doses (2, 5, 15, 30 g/kg) to mixed groupsof patients. Concentration profiles for the four simulated doses reveal a rather good consistency withexperimental data.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11368/2891412
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