Physiological Parameters and Databases for PBPK Modeling

Background: Physiologically based pharmacokinetic (PBPK) modeling and simulating may be a powerful tool in predicting drug behaviors in specific populations. It is a mathematical model that relates the pharmacokinetic (PK) profile of a compound with human anatomical characteristics, physiological characteristics, and biochemical parameters. Predictions using PBPK models offer a promising way to guide drug development and can be used to optimize clinical dosing regimens. However, PK data of new drugs in the pediatric population are too limited to guide clinical therapy, which may lead to frequent adverse events or insufficient efficacy for pediatric patients, particularly in neonates and infants.Objective: The objective of this study was to establish a virtual Chinese pediatric population based on the physiological parameters of Chinese children that could be utilized in PBPK models.Methods: A Chinese pediatric PBPK model was developed in Simcyp Simulator by collecting published Chinese pediatric physiological and anthropometric data to use as system parameters. This pediatric population model was then evaluated in the Chinese pediatric population by predicting the pharmacokinetic characteristics of four probe drugs: theophylline (major CYP1A2 substrate), fentanyl (major CYP3A4 substrate), vancomycin, and ceftazidime (renal-eliminated).Results: The predicted maximum concentration (Cmax), area under the curve of concentration-time (AUC), and clearance (CL) for theophylline (CYP1A2 metabolism pathway) and fentanyl (CYP3A4 metabolism pathway) were within two folds of the observed data. For drugs mainly eliminated by renal clearance (vancomycin and ceftazidime) in the Chinese pediatric population, the ratio of prediction to observation for major PK parameters was within a 2-fold error range.Conclusion: The model is a supplement to the previous Chinese population PBPK model. We anticipate the model to be a better representative of the pediatric Chinese population for drugs PK, offering greater clinical precision for medication given to the pediatric population, ultimately advancing clinical development of pediatric drugs. We can refine this model further by collecting more physiological parameters of Chinese children.

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First-Person Experiments in Thinking

European Psychologist ◽

10.1027/1016-9040/a000301 ◽

2018 ◽

Vol 23 (3) ◽

pp. 189-205 ◽

Cited By ~ 8

Author(s):

Renatus Ziegler ◽

Ulrich Weger

Keyword(s):

Physiological Parameters ◽

The Self ◽

First Person ◽

Psychological Phenomena ◽

Third Person ◽

Current Article ◽

Thinking Process ◽

Mental Contents

Abstract. In psychology, thinking is typically studied in terms of a range of behavioral or physiological parameters, focusing, for instance, on the mental contents or the neuronal correlates of the thinking process proper. In the current article, by contrast, we seek to complement this approach with an exploration into the experiential or inner dimensions of thinking. These are subtle and elusive and hence easily escape a mode of inquiry that focuses on externally measurable outcomes. We illustrate how a sufficiently trained introspective approach can become a radar for facets of thinking that have found hardly any recognition in the literature so far. We consider this an important complement to third-person research because these introspective observations not only allow for new insights into the nature of thinking proper but also cast other psychological phenomena in a new light, for instance, attention and the self. We outline and discuss our findings and also present a roadmap for the reader interested in studying these phenomena in detail.

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