A guide to developing population files for physiologically-based pharmacokinetic modeling in the Simcyp Simulator.

Publisher: Wiley Country of Publication: United States NLM ID: 101580011 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2163-8306 (Electronic) Linking ISSN: 21638306 NLM ISO Abbreviation: CPT Pharmacometrics Syst Pharmacol Subsets: MEDLINE

Publication: 2015- : Hoboken, NJ : Wiley
Original Publication: New York, NY : Nature Pub. Group

Models, Biological* ; Computer Simulation* ; Software* ; Pharmacokinetics*; Humans ; Crohn Disease/metabolism ; Obesity/metabolism ; Obesity, Morbid/metabolism ; Pharmaceutical Preparations/metabolism ; Drug Development/methods

The Simcyp Simulator is a software platform widely used in the pharmaceutical industry to conduct stochastic physiologically-based pharmacokinetic (PBPK) modeling. This approach has the advantage of combining routinely generated in vitro data on drugs and drug products with knowledge of biology and physiology parameters to predict a priori potential pharmacokinetic changes in absorption, distribution, metabolism, and excretion for populations of interest. Combining such information with pharmacodynamic knowledge of drugs enables planning for potential dosage adjustment when clinical studies are feasible. Although the conduct of dedicated clinical studies in some patient groups (e.g., with hepatic or renal diseases) is part of the regulatory path for drug development, clinical studies for all permutations of covariates potentially affecting pharmacokinetics are impossible to perform. The role of PBPK in filling the latter gap is becoming more appreciated. This tutorial describes the different input parameters required for the creation of a virtual population giving robust predictions of likely changes in pharmacokinetics. It also highlights the considerations needed to qualify the models for such contexts of use. Two case studies showing the step-by-step development and application of population files for obese or morbidly obese patients and individuals with Crohn's disease are provided as the backbone of our tutorial to give some hands-on and real-world examples.
(© 2024 The Author(s). CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

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0 (Pharmaceutical Preparations)

Date Created: 20240720 Date Completed: 20241104 Latest Revision: 20241106

20241106

PMC11533108

10.1002/psp4.13202

39030888