Modeling Drug Disposition and Drug–Drug Interactions Through Hypothesis-Driven Physiologically Based Pharmacokinetics: a Reversal Translation Perspective
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A crucial feature of physiologically based pharmacokinetic (PBPK) modeling is the ability to separate compound-dependent properties from population-dependent properties, enabling prospective prediction of compound exposure and disposition in a specific population by accounting for the demographic, physiological, and biological information of the population of interest. The impact of PBPK modeling for prospective prediction relies heavily on predictive accuracy, which is challenged by the scarcity of system-specific physiological or biological data, the quality of compound data measured from in vitro experiments, and the mechanistic understanding of processes governing the pharmacokinetics. It is, therefore, vital to regularly revisit and update the PBPK model for a special population, such as neonates and infants [1, 2], individuals of various ethnicities [3, 4], patients with renal impairment [5, 6], patients with chronic heart failure , or patients with cancer ,...
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The authors have no conflicts of interest to declare.
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