Chronic kidney disease and physiologically based pharmacokinetic modeling: a critical review of existing models

• Published in: Expert opinion on drug metabolism & toxicology Vol. 20; no. 1-2; p. 95
• Main Authors: Zamir, Ammara, Alqahtani, Faleh, Rasool, Muhammad Fawad
• Format: Journal Article
• Language: English
• Published: England 2024
• Subjects: Child; Computer Simulation; Glomerular Filtration Rate; Humans; Models, Biological; Renal Insufficiency, Chronic; pharmacokinetics; renal clearance; model evaluation; Chronic kidney disease (CKD); physiologically based pharmacokinetic modeling (PBPK); pathophysiology
• DOI: 10.1080/17425255.2024.2311154

Physiologically based pharmacokinetic (PBPK) modeling is a paradigm shift in this era for determining the exposure of drugs in pediatrics, geriatrics, and patients with chronic diseases where clinical trials are difficult to conduct. This review has collated data regarding published PBPK models on chronic kidney disease (CKD), including the drug and system-specific input model parameters and model evaluation criteria. Four databases were used from 13th June 2023 to 10 July 2023 for identifying the relevant studies that met the inclusion/exclusion criteria. Alterations in plasma protein (albumin/alpha-1 acid glycoprotein), gastric emptying time, hematocrit, small intestinal transit time, the abundance of cytochrome (CYP) 450 enzymes, glomerular filtration rate, and physicochemical parameters for different drugs were explicitly elaborated from earlier reported studies. Moreover, model evaluation depicted that models in CKD for most of the included drugs were within the allowed two-fold error range. This review will provide insights for researchers on applying PBPK models in managing patients with different levels of CKD to prevent undesirable side effects and increase the effectiveness of drug therapy.